Charles Yu MD is an Assistant Professor of Ophthalmology at the Byers Eye Institute at Stanford. He is from San Francisco and received his undergraduate degree from the University of California Berkeley, his medical degree from University of California Davis, and completed ophthalmology residency at Stanford University. He also completed both a research and a clinical fellowship in the subspecialty of Cornea and Refractive Surgery at Weill Cornell Medical College in New York City. Prior to returning to Stanford, Dr. Yu was an Assistant Professor at the Illinois Eye and Ear Infirmary in Chicago for several years.
Dr. Yu is a board certified ophthalmologist and fellow of the American Academy of Ophthalmology. In addition to treating patients with cataract, cornea and other anterior segment disorders, he teaches residents and leads an active research laboratory focused on developing new treatments for cornea blindness. His research is supported by the National Eye Institute and the U.S. Department of Defense.
Assistant Professor - Med Center Line, Ophthalmology
Honors & Awards
Vision Research Program, U.S. Department of Defense (2019)
Dean's Clinical Translational Research Award, University of Illinois Chicago (2018)
K08 Early Career Award, National Eye Institute (2017)
Golden Apple Teaching Award, Illinois Eye and Ear Infirmary (2016)
Eversight Research Award, Eversight (2015)
K12 Scholar, University of Illinois Chicago (2015)
Member, Alpha Omega Alpha (2010)
Regents Scholar, University of California (2009)
Medical Education: University of California Davis School of Medicine (2010) CA
Board Certification: American Board of Ophthalmology, Ophthalmology (2016)
Fellowship: Weill Cornell Medical College Dept of Ophthalmology (2015) NY
Residency: Stanford University Ophthalmology Residency (2014) CA
Internship: Santa Clara Valley Medical Center Dept of Medicine (2011) CA
Current Research and Scholarly Interests
Corneal opacity is a leading cause of blindness. Cornea transplantation is at high risk of rejection when there is pre-existing vascularization of the cornea and in pediatric patients. Cornea transplant shortage remains a worldwide problem with millions on waitlists. Our laboratory is developing multiple strategies for treatment of corneal blindness. We are testing advanced materials and designs for keratoprostheses with the goal of reducing complications and easing surgical implantation. We are also developing intraocular electronic display prostheses for bypassing cornea opacity, a novel strategy that could allow for high quality vision without corneal clarity.
Transgenic models for investigating the nervous system: Currently available neurofluorescent reporters and potential neuronal markers.
Biochimica et biophysica acta. General subjects
Recombinant DNA technologies have enabled the development of transgenic animal models for use in studying a myriad of diseases and biological states. By placing fluorescent reporters under the direct regulation of the promoter region of specific marker proteins, these models can localize and characterize very specific cell types. One important application of transgenic species is the study of the cytoarchitecture of the nervous system. Neurofluorescent reporters can be used to study the structural patterns of nerves in the central or peripheral nervous system in vivo, as well as phenomena involving embryologic or adult neurogenesis, injury, degeneration, and recovery. Furthermore, crucial molecular factors can also be screened via the transgenic approach, which may eventually play a major role in the development of therapeutic strategies against diseases like Alzheimer's or Parkinson's. This review describes currently available reporters and their uses in the literature as well as potential neural markers that can be leveraged to create additional, robust transgenic models for future studies.
View details for DOI 10.1016/j.bbagen.2020.129595
View details for PubMedID 32173376
Thermal analysis of intraocular electronic display projector visual prosthesis
Numerical Heat Transfer, Part A: Applications
2020; 78 (5)
View details for DOI 10.1080/10407782.2020.1805230
Characterization of an Electronic Corneal Prosthesis System.
Current eye research
PurposeCorneal opacity is a leading cause of reversible blindness worldwide. An electronic corneal prosthesis, or intraocular projector, could potentially restore high-quality vision without need for corneal clarity.Materials and MethodsFour intraocular projection systems were constructed from commercially available electronic components and encased in biocompatible plastic housing. They were tested for optical properties, biocompatibility, heat dissipation, waterproofing and accelerated wear. A surgical implantation technique was developed.ResultsIntraocular projectors were produced of a size that can fit within the eye. Their optics produce better than 20/200 equivalent visual acuity. MTT assay demonstrated no cytotoxicity of devices in vitro. Temperature testing demonstrated less than 2° C increase in temperature after one hour. 3 devices lasted over 12 weeks under accelerated wear conditions. Implantation surgery was demonstrated via corneal trephination insertion in a cadaver eye.ConclusionThis is the first study to demonstrate and characterize fully functional intraocular projection systems. This technology has the potential to be an important new tool in the treatment of intractable corneal blindness.
View details for DOI 10.1080/02713683.2019.1708957
View details for PubMedID 31886728
- Feasibility of Intraocular Projection for Treatment of Intractable Corneal Opacity CORNEA 2019; 38 (4): 523–27
- Season and Allergic Conjunctivitis Cornea: Fundamentals, Diagnosis and Management Elsevier. 2019; 4: 526–532
Late detachment of Descemet's membrane after penetrating keratoplasty for pellucid marginal degeneration.
American journal of ophthalmology case reports
2019; 13: 151–53
we report a case of late spontaneous large detachment of Descemet's membrane in recurrent pellucid marginal degeneration after penetrating keratoplasty.a 73-year-old man presented to clinic with spontaneous detachment of his Descemet's membrane 30 years after penetrating keratoplasty for pellucid marginal degeneration. Efforts were made to bubble the membrane back into place without success. The patient then underwent endothelial keratoplasty with successful restoration of cornea clarity.this condition may cause diagnostic and treatment dilemmas if not properly identified and managed. In addition this case has information for both the use of scleral contact lens and the success of endothelial keratoplasty in an extremely steep cornea.
View details for DOI 10.1016/j.ajoc.2018.12.016
View details for PubMedID 30766935
View details for PubMedCentralID PMC6350212
Fluorescent reporter transgenic mice for in vivo live imaging of angiogenesis and lymphangiogenesis.
The study of lymphangiogenesis is an emerging science that has revealed the lymphatic system as a central player in many pathological conditions including cancer metastasis, lymphedema, and organ graft rejection. A thorough understanding of the mechanisms of lymphatic growth will play a key role in the development of therapeutic strategies against these conditions. Despite the known potential of this field, the study of lymphatics has historically lagged behind that of hemangiogenesis. Until recently, significant strides in lymphatic studies were impeded by a lack of lymphatic-specific markers and suitable experimental models compared to those of the more immediately visible blood vasculature. Lymphangiogenesis has also been shown to be a key phenomenon in developmental biological processes, such as cell proliferation, guided migration, differentiation, and cell-to-cell communication, making lymphatic-specific visualization techniques highly desirable and desperately needed. Imaging modalities including immunohistochemistry and in situ hybridization are limited by the need to sacrifice animal models for tissue harvesting at every experimental time point. Moreover, the processes of mounting and staining harvested tissues may introduce artifacts that can confound results. These traditional methods for investigating lymphatic and blood vasculature are associated with several problems including animal variability (e.g., between mice) when replicating lymphatic growth environments and the cost concerns of prolonged, labor-intensive studies, all of which complicate the study of dynamic lymphatic processes. With the discovery of lymphatic-specific markers, researchers have been able to develop several lymphatic and blood vessel-specific, promoter-driven, fluorescent-reporter transgenic mice for visualization of lymphatics in vivo and in vitro. For instance, GFP, mOrange, tdTomato, and other fluorescent proteins can be expressed under control of a lymphatic-specific marker like Prospero-related homeobox 1 (Prox1), which is a highly conserved transcription factor for determining embryonic organogenesis in vertebrates that is implicated in lymphangiogenesis as well as several human cancers. Importantly, Prox1-null mouse embryos develop without lymphatic vessels. In human adults, Prox1 maintains lymphatic endothelial cells and upregulates proteins associated with lymphangiogenesis (e.g., VEGFR-3) and downregulates angiogenesis-associated gene expression (e.g., STAT6). To visualize lymphatic development in the context of angiogenesis, dual fluorescent-transgenic reporters, like Prox1-GFP/Flt1-DsRed mice, have been bred to characterize lymphatic and blood vessels simultaneously in vivo. In this review, we discuss the trends in lymphatic visualization and the potential usage of transgenic breeds in hemangiogenesis and lymphangiogenesis research to understand spatial and temporal correlations between vascular development and pathological progression.
View details for DOI 10.1007/s10456-018-9629-2
View details for PubMedID 29971641
3D printing for low cost, rapid prototyping of eyelid crutches.
Orbit (Amsterdam, Netherlands)
Blepharoptosis or ptosis is a common and potentially debilitating clinical problem. Long-term surgical treatment for ptosis caused by progressive myopathies can be challenging due to potential recurrence and complications associated with facial muscle weakness. When surgical treatment is no longer effective, an eyelid crutch can be used as an alternative intervention. This report demonstrates how 3D printing was used to rapidly design, prototype, and manufacture new custom-fit eyelid crutches at a low cost.
View details for DOI 10.1080/01676830.2018.1445760
View details for PubMedID 29498564
Potential lymphangiogenesis therapies: Learning from current antiangiogenesis therapies-A review.
Medicinal research reviews
In recent years, lymphangiogenesis, the process of lymphatic vessel formation from existing lymph vessels, has been demonstrated to have a significant role in diverse pathologies, including cancer metastasis, organ graft rejection, and lymphedema. Our understanding of the mechanisms of lymphangiogenesis has advanced on the heels of studies demonstrating vascular endothelial growth factor C as a central pro-lymphangiogenic regulator and others identifying multiple lymphatic endothelial biomarkers. Despite these breakthroughs and a growing appreciation of the signaling events that govern the lymphangiogenic process, there are no FDA-approved drugs that target lymphangiogenesis. In this review, we reflect on the lessons available from the development of antiangiogenic therapies (26 FDA-approved drugs to date), review current lymphangiogenesis research including nanotechnology in therapeutic drug delivery and imaging, and discuss molecules in the lymphangiogenic pathway that are promising therapeutic targets.
View details for DOI 10.1002/med.21496
View details for PubMedID 29528507
Iris suture fixation: Push-knot needle.
Journal of cataract and refractive surgery
2017; 43 (4): 456-458
We describe a technique to create a locking knot for iris reconstruction or intraocular lens fixation. A modified needle is prepared by straightening the tip of an ophthalmic viscosurgical device needle or a lacrimal cannula needle. After the suture is passed through 2 sides of an iris defect, the 2 ends are externalized and looped. One strand is then inserted into the needle from the tip out of the ferrule, and the knot is pushed into the anterior chamber by this needle in a controllable manner. Two other locking knots are then made by repeating the process. With this method, only 1 small corneal incision is necessary regardless of the number of knots required and only a small amount of anterior chamber space is needed during the knotting process.
View details for DOI 10.1016/j.jcrs.2017.04.004
View details for PubMedID 28532928
Subjective Quality of Vision After Myopic LASIK: Prospective 1-Year Comparison of Two Wavefront-Guided Excimer Lasers.
Journal of refractive surgery
2016; 32 (4): 224-229
To compare subjective quality of vision between two wavefront-guided lasers in the treatment of myopia up to 1 year postoperatively.In this prospective randomized study, 100 eyes of 50 patients were treated with wavefront-guided LASIK. One eye was treated with the WaveLight Allegretto Wave Eye-Q 400-Hz excimer laser (Alcon Laboratories, Inc., Hünenberg, Switzerland) and the other was treated with the VISX Star S4 IR CustomVue excimer laser (Abbott Medical Optics, Santa Ana, CA). Patients completed a questionnaire assessing quality of vision and visual symptoms preoperatively and at postoperative months 1, 3, 6, and 12.The Allegretto system demonstrated non-statistically significant superiority in several subjective parameters as early as 1 month after surgery. At 12 months, there was better clarity during the day (P = .001) in the Allegretto group. Subgroup analyses were performed on eyes with preoperative higher order aberrations of 0.3 µm or less and in patients with preoperative higher order aberrations greater than 0.3 µm. In subgroup analysis, there were no differences between the two systems in eyes with low higher order aberrations or high higher order aberrations. Patients did not express any preference for one system over the other when surveyed at 1 year postoperatively.One year after surgery, there were no differences in self-reported quality of vision outcomes with the exception of better clarity of vision during the day in the eyes treated with the Allegretto system. Patients did not express any preference for one treatment modality over the other. [J Refract Surg. 2016;32(4):224-229.].
View details for DOI 10.3928/1081597X-20151222-03
View details for PubMedID 27070228
Biocompatibility of poly(ethylene glycol) and poly(acrylic acid) interpenetrating network hydrogel by intrastromal implantation in rabbit cornea.
Journal of biomedical materials research. Part A
2015; 103 (10): 3157-3165
We evaluated the biocompatibility of a poly(ethylene glycol) and poly(acrylic acid) (PEG/PAA) interpenetrating network hydrogel designed for artificial cornea in a rabbit model. PEG/PAA hydrogel measuring 6 mm in diameter was implanted in the corneal stroma of twelve rabbits. Stromal flaps were created with a microkeratome. Randomly, six rabbits were assigned to bear the implant for 2 months, two rabbits for 6 months, two rabbits for 9 months, one rabbit for 12 months, and one rabbit for 16 months. Rabbits were evaluated monthly. After the assigned period, eyes were enucleated, and corneas were processed for histology and immunohistochemistry. There were clear corneas in three of six rabbits that had implantation of hydrogel for 2 months. In the six rabbits with implant for 6 months or longer, the corneas remained clear in four. There was a high rate of epithelial defect and corneal thinning in these six rabbits. One planned 9-month rabbit developed extrusion of implant at 4 months. The cornea remained clear in the 16-month rabbit but histology revealed epithelial in-growth. Intrastromal implantation of PEG/PAA resulted in a high rate of long-term complications. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 3157-3165, 2015.
View details for DOI 10.1002/jbm.a.35453
View details for PubMedID 25778285
Comparison of 2 femtosecond lasers for flap creation in myopic laser in situ keratomileusis: One-year results.
Journal of cataract and refractive surgery
2015; 41 (4): 740-748
To compare laser in situ keratomileusis (LASIK) outcomes between 2 femtosecond lasers for flap creation in the treatment of myopia up to 1 year.University eye clinic.Prospective randomized eye-to-eye study.Consecutive myopic patients were treated with wavefront-guided LASIK. One eye had a flap created by the Intralase FS 60 kHz femtosecond laser, and the fellow eye was treated with the Intralase iFS 150 kHz femtosecond laser. Eyes were randomized according to ocular dominance. Evaluations included measurement of uncorrected distance visual acuity (UDVA), corrected distance visual acuity, contrast sensitivity and wavefront aberrometry.The study enrolled 122 eyes of 61 patients. The mean preoperative spherical equivalent refraction was -4.62 diopters (D) ± 2.32 (SD) and -4.66 ± 2.30 D in the 150 kHz group and 60 kHz group, respectively. Patients preferred the 150 kHz laser to the 60 kHz laser intraoperatively (52.5% versus 26.2%) (P = .005). One week postoperatively, UDVA was 20/16 or better in 85.2% in the 150 kHz group and 70.5% in the 60 kHz group; the difference was statistically significant (P < .05). At 12 months, there were no significant differences in refractive outcomes or higher-order aberrations between the 2 groups.Flap creation with the 150 kHz system and the 60 kHz system resulted in excellent LASIK outcomes. Intraoperatively, patients preferred the 150 kHz system, which yielded better UDVA in the early postoperative period. There were no significant differences at 1 year between the 2 laser systems.Proprietary or commercial disclosures are listed after the references.
View details for DOI 10.1016/j.jcrs.2014.06.038
View details for PubMedID 25840298
Day 1 Wavefront Aberrometry for Prediction of Refractive Outcomes at Year 1 in Myopic LASIK
JOURNAL OF REFRACTIVE SURGERY
2015; 31 (3): 170-174
To determine amount of change in wavefront aberrometric measurements from 1 day to 1 year after myopic LASIK.One hundred five eyes of 105 patients underwent wavefront-guided LASIK. Objective wavefront aberrometric refractions were recorded preoperatively, at postoperative day 1, and at postoperative year 1. Subjective manifest refractions were also collected at postoperative year 1.When comparing objective wavefront aberrometric refractions at postoperative year 1 to postoperative day 1, there was a mean 0.33 diopter spherical equivalent myopic shift. There was no significant difference in the number of eyes within 1.00 diopter of emmetropia spherical equivalent measured by wavefront aberrometric refraction at postoperative day 1 or year 1. There was a correlation of R(2) = 0.14 between degree of preoperative myopia and myopic shift. Higher-order aberrations were overall not increased at day 1 but increased significantly by year 1. Objective aberrometric refractions at postoperative day 1 can be useful in prediction of long-term refractive outcomes.There is a small myopic shift and an increase in higher-order aberrations when comparing wavefront aberrometry results at postoperative day 1 with those at postoperative 1 year.
View details for DOI 10.3928/1081597X-20150220-04
View details for Web of Science ID 000352490700005
View details for PubMedID 25751833
Successful DMEK After Intraoperative Graft Inversion
2015; 34 (1): 97-98
Hardiness of a Descemet membrane endothelial keratoplasty (DMEK) graft is not well established. The aim of this study was to report a case of graft survival after intraoperative inversion.We describe a case of a 76-year-old man with Fuchs corneal dystrophy who underwent DMEK in the left eye. After deployment of the graft and a 15-minute sulfur hexafluoride gas fill, the graft was noted to be inverted. The graft was then reoriented and properly positioned.Because of progressive graft detachment, rebubble was required at 2 weeks after surgery. At 2 months after surgery, the graft was clear and fully adherent. Specular microscopy revealed 27.9% endothelial cell loss of the donor cornea.Despite intraoperative inversion, this DMEK graft remained viable without excessive endothelial cell loss.
View details for PubMedID 25411936
Mobile Virtual Reality for Ophthalmic Image Display and Diagnosis
Journal of Mobile Technology in Medicine
2015; 4 (3): 35–38
View details for DOI 10.7309/jmtm.4.3.7
Subretinal fluid is common in experimental non-arteritic anterior ischemic optic neuropathy
2014; 28 (12): 1494-1501
Anterior ischemic optic neuropathy (AION) is an important cause of acute vision loss for which several animal models exist. It has been associated with subretinal fluid in a previous study on patients but not yet so in animal models.A patient presented with acute non-arteritic AION (NAION) and underwent ophthalmic evaluation and testing including fluorescein angiography and spectral-domain optical coherence tomography (SD-OCT). On the basis of the patient's findings, we used SD-OCT circular and volume scans to analyze retinal changes in a murine model of NAION.One week after left eye vision loss, the patient had clinical and imaging findings consistent with NAION. On SD-OCT, there was prominent peripapillary retinal thickening consistent with intra-retinal edema and sub-foveolar fluid. Inspired by the findings in human AION, we looked for similar changes in murine NAION using SD-OCT. The circular scan did not adequately detect the presence of subretinal fluid. Using the 25-line scan, which covered a larger part of the posterior pole, we found that 100% of murine AION resulted in subretinal fluid at day 1. The subretinal fluid resolved by week 1.This study detailed a case of clinical NAION associated with intra-retinal and subretinal fluid. We also found that subretinal fluid was common in murine photochemical thrombosis model of AION and could be found far away from the optic disc.
View details for DOI 10.1038/eye.2014.220
View details for Web of Science ID 000346365600014
View details for PubMedID 25257770
View details for PubMedCentralID PMC4268460
A Comparison of LASIK Flap Thickness and Morphology Between the Intralase 60-and 150-kHz Femtosecond Lasers
JOURNAL OF REFRACTIVE SURGERY
2014; 30 (12): 827-830
To prospectively compare the achieved thickness and consistency of LASIK flaps created with a 60- and 150-kHz femtosecond laser.One hundred twenty eyes of 60 patients with myopia were treated with LASIK. One eye had flap created by the Intralase FS 60-kHz femtosecond laser (Abbott Medical Optics, Abbott Park, IL) and the fellow eye was treated with the IntraLase iFS 150-kHz femtosecond laser (Abbott Medical Optics). Eyes were randomized according to ocular dominance. Flap morphology and measurements were taken with anterior segment optical coherence tomography (AS-OCT) at the 1-month postoperative visit.AS-OCT showed similar regular planar morphologies in both groups. The mean thickness of the flaps in the FS 60 group was significantly higher than that of the iFS 150 group (105.4 ± 3.9 μm vs 103.9 ± 4.8 μm, P = .009). The mean deviation from targeted flap thickness was not significantly different between the two groups.The Intralase iFS 150-kHz femtosecond laser creates flaps of similar thickness and uniformity to the Intralase FS 60-kHz femtosecond laser.
View details for DOI 10.3928/1081597X-20141113-04
View details for Web of Science ID 000347475200008
View details for PubMedID 25437481
Prevention and treatment of injection-related endophthalmitis
GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
2014; 252 (7): 1027-1031
Intravitreal injections are the fastest growing cause of endophthalmitis and can result in severe vision loss. The prevention, diagnosis and management of such infections remain unclear and at times controversial.We searched Pubmed for keywords "prophylaxis," "endophthalmitis," "intravitreal injection." We focused on studies published in the last 2 years as well as other recent studies with particular attention to data on the incidence, microbiology, prevention, and treatment of injection-related endophthalmitis.Over 20 relevant studies were found. With povidone-iodine preparation, the per-injection endophthalmitis rate is low at about 0.03%. Antibiotics do not appear to be beneficial for prevention of post-injection endophthalmitis. The best timing of vitrectomy is unclear.Antibiotic prophylaxis is probably not needed when giving intravitreal injections. More data is needed to help determine the proper treatment for post-injection endophthalmitis.
View details for DOI 10.1007/s00417-014-2644-0
View details for PubMedID 24807232
Comparison of 2 wavefront-guided excimer lasers for myopic laser in situ keratomileusis: One-year results
JOURNAL OF CATARACT AND REFRACTIVE SURGERY
2014; 40 (3): 412-422
To compare laser in situ keratomileusis (LASIK) outcomes between 2 wavefront-guided excimer laser systems in the treatment of myopia.University eye clinic, Palo Alto, California, USA.Prospective comparative case series.One eye of patients was treated with the Allegretto Wave Eye-Q system (small-spot scanning laser) and the fellow eye with the Visx Star Customvue S4 IR system (variable-spot scanning laser). Evaluations included measurement of uncorrected visual acuity, corrected visual acuity, and wavefront aberrometry.One hundred eyes (50 patients) were treated. The mean preoperative spherical equivalent (SE) refraction was -3.89 diopters (D) ± 1.67 (SD) and -4.18 ± 1.73 D in the small-spot scanning laser group and variable-spot scanning laser group, respectively. There were no significant differences in preoperative higher-order aberrations (HOAs) between the groups. Twelve months postoperatively, all eyes in the small-spot scanning laser group and 92% in the variable-spot scanning laser group were within ±0.50 D of the intended correction (P = .04). At that time, the small-spot scanning laser group had significantly less spherical aberration (0.12 versus 0.15) (P = .04) and significantly less mean total higher-order root mean square (0.33 μm versus 0.40 μm) (P = .01). Subjectively, patients reported that the clarity of night and day vision was significantly better in the eye treated with the small-spot scanning laser.The predictability and self-reported clarity of vision of wavefront-guided LASIK were better with the small-spot scanning laser. Eyes treated with the small-spot scanning laser had significantly fewer HOAs.
View details for DOI 10.1016/j.jcrs.2013.08.050
View details for PubMedID 24581773
Prevention of postcataract endophthalmitis: evidence-based medicine
CURRENT OPINION IN OPHTHALMOLOGY
2012; 23 (1): 19-25
To provide a summary of current peer-reviewed publications on the methods of prophylaxis against postcataract endophthalmitis.Preoperative application of povidone-iodine remains the standard protocol for the prevention of postoperative endophthalmitis. More recent evidence suggests that intracameral cefuroxime administered at the conclusion of surgery significantly reduces the risk of endophthalmitis. However, its clinical use has been limited because of a lack of commercially available antibiotic indicated for intraocular injection. Although topical antibiotic application continues to be a controversial topic with respect to the types of antibiotic prescribed and dosage, most ophthalmologists do prescribe an antibiotic for the perioperative period. Resistance against antibiotics, including the very popular classes of fluoroquinolones, is rising. Most notably, methicillin resistance continues to increase over time.Prevention of postcataract endophthalmitis remains a difficult topic to study given the low incidence. In addition to appropriate wound construction, a combination of povidone-iodine and antibiotics provide a reasonable approach in reducing the risk of this rare but serious infection.
View details for DOI 10.1097/ICU.0b013e32834cd5a9
View details for Web of Science ID 000298150700005
View details for PubMedID 22081026
- Feeding the vertebrate retina from the Cambrian to the Tertiary JOURNAL OF ZOOLOGY 2009; 278 (4): 259–69
Vascular endothelial growth factor mediates corneal nerve repair
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
2008; 49 (9): 3870-3878
To examine the expression of vascular endothelial growth factor (VEGF) and its receptors in the cornea and the trigeminal ganglion and to characterize the role of VEGF in mediating corneal nerve repair.Regeneration of the corneal subbasal nerve plexus after epithelial debridement was measured. The expression of VEGF and its receptors was examined in the trigeminal ganglia and in the cornea by RT-PCR, immunohistochemistry, and Western blotting. VEGF-mediated nerve growth was measured in a trigeminal ganglia explant assay. Anti-VEGF neutralizing antibody was used to examine the VEGF-dependent growth of neurons in vitro and regeneration of the corneal nerves in vivo.After two distinct patterns of nerve regeneration, the subbasal nerves recovered to 65% of the preinjury density after 28 days. RT-PCR demonstrated gene expression of VEGF and VEGF receptors in the trigeminal ganglia. Immunohistochemistry showed staining for VEGF and its receptors in the trigeminal ganglia and for VEGFR1, VEGFR2, and neuropilin (NRP)-1 in the cornea. Western blot confirmed these results. In vitro, VEGF promoted the growth of explanted trigeminal ganglia by 91%. Blockage of VEGF signaling with anti-VEGF antibody reduced the growth of cultured neurons by 17% and the regeneration of subbasal neurons by 23%.In addition to providing new information on the regeneration of murine corneal nerves, this study presents evidence that VEGF signaling influences the repair of corneal nerves by demonstrating that VEGF and VEGF receptors are present in the trigeminal ganglia and that abrogation of VEGF signaling reduces nerve growth in vitro and in vivo.
View details for DOI 10.1167/iovs.07-1418
View details for Web of Science ID 000258896500018
View details for PubMedID 18487369
View details for PubMedCentralID PMC3725763
Transgenic corneal neurofluorescence in mice: A new model for in vivo investigation of nerve structure and regeneration
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
2007; 48 (4): 1535-1542
To quantify the level of neuron-specific fluorescence in the corneas of transgenic mice expressing yellow fluorescent protein (YFP) driven by the thy1 promoter and examine the viability of using thy1-YFP mice as a model for studying nerve regeneration in vivo.The structure of corneal innervation in thy1-YFP mice visible with reporter gene fluorescence was compared with that visible with traditional immunofluorescence techniques. The percentage of corneal nerves with YFP fluorescence in wholemounted corneas and trigeminal neuron cultures was determined. Regeneration of fluorescent corneal neuronal processes after wounding was monitored in vivo.In the mouse cornea, neuron-specific immunostaining determined that nerves enter the stroma in several bundles that then extend throughout the entire cornea. These stromal nerve bundles form a subbasal plexus beneath the corneal epithelium. Fine nerves from this plexus travel superficially to the ocular surface. Neuron-specific expression of YFP allowed visualization of nearly all large nerve bundles of the stroma but only some of the many finer nerves of the subbasal plexus and surface. In the subbasal nerve plexus, 46% of total neuronal processes exhibited YFP neurofluorescence. In vitro, 22% of cultured trigeminal neurons exhibited YFP neurofluorescence. After corneal nerve transection, nerve processes distal to the site of injury degenerated, whereas those proximal to the site regenerated in a pattern different from original nerve architecture.Thy1-YFP mice display neurofluorescence and provide a novel model for monitoring the patterning, injury, and growth of corneal nerves in vivo.
View details for DOI 10.1167/iovs.06-1192
View details for Web of Science ID 000245408200015
View details for PubMedID 17389482