All Publications

  • Out of darkness PALLIATIVE & SUPPORTIVE CARE Xu, C. L. 2021; 19 (4): 509-510
  • Ode to a good neighbor. Palliative & supportive care Xu, C. L. 2021: 1

    View details for DOI 10.1017/S1478951521000201

    View details for PubMedID 33658097

  • Comparison of structural progression between ciliopathy and non-ciliopathy associated with autosomal recessive retinitis pigmentosa Xu, C. L., Takahashi, V., Ben Apatoff, M., Takiuti, J., Duong, J. K., Mahajan, V. B., Tsang, S. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2019
  • Fundus autofluorescence and ellipsoid zone (EZ) line width can be an outcome measurement in RHO-associated autosomal dominant retinitis pigmentosa. Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie Takahashi, V. K., Takiuti, J. T., Carvalho-Jr, J. R., Xu, C. L., Duong, J. K., Mahajan, V. B., Tsang, S. H. 2019


    PURPOSE: To evaluate the progression of retinitis pigmentosa (RP) due to mutations in rhodopsin (RHO) by measuring the short-wavelength autofluorescence (SW-AF) increased autofluorescence ring and ellipsoid zone (EZ)-line width.METHODS: Fundus autofluorescence (FAF) and spectral domain optical coherence tomography (SD-OCT) images were obtained from 10 patients with autosomal dominant RP due to mutations in the RHO gene. Measurements of ring area on FAF images, as well as the EZ line width on SD-OCT images and horizontal, vertical diameter, were performed by two independent masked graders.RESULTS: The ring area decreased by a rate of 0.6±0.2mm2 per year. We observed that the EZ line width decreased by an average of 152±37mum per year, while the horizontal and vertical diameters decreased by 106±35mum and 125±29mum per year, respectively. Progression rates were similar between eyes.CONCLUSIONS: We observed SW-AF ring constriction and a progressive loss of EZ line width over time.

    View details for PubMedID 30635721

  • Viral Delivery Systems for CRISPR. Viruses Xu, C. L., Ruan, M. Z., Mahajan, V. B., Tsang, S. H. 2019; 11 (1)


    The frontiers of precision medicine have been revolutionized by the development of Clustered Regularly-Interspaced Short Palindromic Repeats (CRISPR)/Cas9 as an editing tool. CRISPR/Cas9 has been used to develop animal models, understand disease mechanisms, and validate treatment targets. In addition, it is regarded as an effective tool for genome surgery when combined with viral delivery vectors. In this article, we will explore the various viral mechanisms for delivering CRISPR/Cas9 into tissues and cells, as well as the benefits and drawbacks of each method. We will also review the history and recent development of CRISPR and viral vectors and discuss their applications as a powerful tool in furthering our exploration of disease mechanisms and therapies.

    View details for PubMedID 30621179

  • Novel REEP6 gene mutation associated with autosomal recessive retinitis pigmentosa. Documenta ophthalmologica. Advances in ophthalmology Lin, Y. n., Xu, C. L., Velez, G. n., Yang, J. n., Tanaka, A. J., Breazzano, M. P., Mahajan, V. B., Sparrow, J. R., Tsang, S. H. 2019


    This study reports the ophthalmic and genetic findings of a Cameroonian patient with autosomal recessive retinitis pigmentosa (arRP) caused by a novel Receptor Expression Enhancing Protein 6 (REEP6) homozygous mutation.A 33-year-old man underwent comprehensive ophthalmic examinations, including visual acuity measurements, dilated fundus imaging, electroretinography (ERG), and spectral-domain optical coherence tomography (SD-OCT). Short-wavelength fundus autofluorescence (SW-AF) and near-infrared fundus autofluorescence (NIR-AF) were also evaluated. Whole exome sequencing (WES) was used to identify potential pathogenic variants.Fundus examination revealed typical RP findings with additional temporal ten micron yellow dots. SD-OCT imaging revealed cystoid macular edema and perifoveal outer retinal atrophy with centrally preserved inner segment ellipsoid zone (EZ) bands. Hyperreflective spots were seen in the inner retinal layers. On SW-AF images, a hypoautofluorescent area in the perifoveal area was observed. NIR-AF imaging revealed an irregularly shaped hyperautofluorescent ring. His visual acuity was mildly affected. ERG showed undetectable rod responses and intact cone responses. Genetic testing via WES revealed a novel homozygous mutation (c.295G>A, p.Glu99Lys) in the gene encoding REEP6, which is predicted to alter the charge in the transmembrane helix.This report is not only the first description of a Cameroonian patient with arRP associated with a REEP6 mutation, but also this particular genetic alteration. Substitution of p.Glu99Lys in REEP6 likely disrupts the interactions between REEP6 and the ER membrane. NIR-AF imaging may be particularly useful for assessing functional photoreceptor cells and show an "avocado" pattern of hyperautofluorescence in patients with the REEP6 mutation.

    View details for DOI 10.1007/s10633-019-09719-1

    View details for PubMedID 31538292

  • Comparison of structural progression between ciliopathy and non-ciliopathy associated with autosomal recessive retinitis pigmentosa. Orphanet journal of rare diseases Takahashi, V. K., Xu, C. L., Takiuti, J. T., Apatoff, M. B., Duong, J. K., Mahajan, V. B., Tsang, S. H. 2019; 14 (1): 187


    To evaluate and compare the progression of ciliopathy and non-ciliopathy autosomal recessive Retinitis Pigmentosa patients (arRP) by measuring the constriction of hyperautofluorescent rings in fundus autofluorescence (FAF) images and the progressive shortening of the ellipsoid zone line width obtained by spectral-domain optical coherence tomography (SD-OCT).For the ciliopathy group, the estimated mean shortening of the ellipsoid zone line was 259 μm per year and the ring area decreased at a rate of 2.46 mm2 per year. For the non-ciliopathy group, the estimated mean shortening of the ellipsoid zone line was 84 μm per year and the ring area decreased at a rate of 0.7 mm2 per year.Our study was able to quantify and compare the loss of EZ line width and short-wavelength autofluorescence (SW-AF) ring constriction progression over time for ciliopathy and non-ciliopathy arRP genes. These results may serve as a basis for modeling RP disease progression, and furthermore, they could potentially be used as endpoints in clinical trials seeking to promote cone and rod survival in RP patients.

    View details for DOI 10.1186/s13023-019-1163-9

    View details for PubMedID 31370859

  • CRISPR Base Editing in Induced Pluripotent Stem Cells. Methods in molecular biology (Clifton, N.J.) Chang, Y. J., Xu, C. L., Cui, X. n., Bassuk, A. G., Mahajan, V. B., Tsai, Y. T., Tsang, S. H. 2019


    Induced pluripotent stem cells (iPSCs) have demonstrated tremendous potential in numerous disease modeling and regenerative medicine-based therapies. The development of innovative gene transduction and editing technologies has further augmented the potential of iPSCs. Cas9-cytidine deaminases, for example, have developed as an alternative strategy to integrate single-base mutations (C → T or G → A transitions) at specific genomic loci. In this chapter, we specifically describe CRISPR (clustered regularly interspaced short palindromic repeats) base editing in iPSCs for editing precise locations in the genome. This state-of-the-art approach enables highly efficient and accurate modifications in genes. Thus, this technique not only has the potential to have biotechnology and therapeutic applications but also the ability to reveal underlying mechanisms regarding pathologies caused by specific mutations.

    View details for DOI 10.1007/7651_2019_243

    View details for PubMedID 31250381

  • Translation of CRISPR Genome Surgery to the Bedside for Retinal Diseases FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY Xu, C. L., Cho, G. Y., Sengillo, J. D., Park, K. S., Mahajan, V. B., Tsang, S. H. 2018; 6: 46


    In recent years, there has been accelerated growth of clustered regularly interspaced short palindromic repeats (CRISPR) genome surgery techniques. Genome surgery holds promise for diseases for which a cure currently does not exist. In the field of ophthalmology, CRISPR offers possibilities for treating inherited retinal dystrophies. The retina has little regenerative potential, which makes treatment particularly difficult. For such conditions, CRISPR genome surgery methods have shown great potential for therapeutic applications in animal models of retinal dystrophies. Much anticipation surrounds the potential for CRISPR as a therapeutic, as clinical trials of ophthalmic genome surgery are expected to begin as early as 2018. This mini-review summarizes preclinical CRISPR applications in the retina and current CRISPR clinical trials.

    View details for PubMedID 29876348