All Publications

  • Oculocerebrorenal Syndrome of Lowe: Characterizations of Ocular Presentation and Management Ma, X., Ning, K., Kowal, T., Sun, Y. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2019
  • The Role of Phosphoinositides in Aqueous Humor Dynamics via Optogenetic Stimulation in the Trabecular Meshwork Alvarado, J., Prosseda, P., Ning, K., Kowal, T., Wang, B., Hu, Y., Sun, Y. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2019
  • Role of inositol phosphatase OCRL in microtubule nucleation: Implications for Oculocerebrorenal Syndrome of Lowe Kowal, T., Wang, B., Prosseda, P., Alvarado, J., He, W., Ning, K., Hu, Y., Sun, Y. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2019
  • Characterization of primary cilia in mouse retina during retinal development Ning, K., Kowal, T., Chang, K., Alvarado, J., Silva, R., Kreymerman, A., Mahajan, V. B., Hu, Y., Sun, Y. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2019
  • Review of Ocular Manifestations of Joubert Syndrome. Genes Wang, S. F., Kowal, T. J., Ning, K., Koo, E. B., Wu, A. Y., Mahajan, V. B., Sun, Y. 2018; 9 (12)


    Joubert syndrome is a group of rare disorders that stem from defects in a sensory organelle, the primary cilia. Affected patients often present with disorders involving multiple organ systems, including the brain, eyes, and kidneys. Common symptoms include breathing abnormalities, mental developmental delays, loss of voluntary muscle coordination, and abnormal eye movements, with a diagnostic "molar tooth" sign observed by magnetic resonance imaging (MRI) of the midbrain. We reviewed the ocular phenotypes that can be found in patients with Joubert syndrome. Ocular motor apraxia is the most frequent (80% of patients), followed by strabismus (74%) and nystagmus (72%). A minority of patients also present with ptosis (43%), chorioretinal coloboma (30%), and optic nerve atrophy (22%). Although mutations in 34 genes have been found to be associated with Joubert syndrome, retinal degeneration has been reported in only 38% of patients. Mutations in AHI1 and CEP290, genes critical to primary cilia function, have been linked to retinal degeneration. In conclusion, Joubert syndrome is a rare pleiotropic group of disorders with variable ocular presentations.

    View details for PubMedID 30518138

  • Review of Ocular Manifestations of Joubert Syndrome GENES Wang, S. F., Kowal, T. J., Ning, K., Koo, E. B., Wu, A. Y., Mahajan, V. B., Sun, Y. 2018; 9 (12)
  • The role of inositol phosphatase OCRL in microtubule nucleation: Implications for Oculocerebrorenal Syndrome of Lowe Wang, B., Prosseda, P. P., He, W., Kowal, T., Alvarado, J. A., Ning, K., Sun, Y. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2018
  • Ocular and renal phenotypes of NPHP1 deletion in Senior Loken syndrome Ning, K., Song, E., Haider, K. M., Ghaffarieh, A., Alvarado, J. A., Sun, Y. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2018
  • Optogenetic Regulation of Aqueous Outflow in Mouse Trabecular Meshwork Alvarado, J. A., Prosseda, P. P., Luo, N., Wang, B., Ning, K., He, W., Kowal, T., Sun, Y. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2018
  • Sleep deprivation disrupts the lacrimal system and induces dry eye disease. Experimental & molecular medicine Li, S., Ning, K., Zhou, J., Guo, Y., Zhang, H., Zhu, Y., Zhang, L., Jia, C., Chen, Y., Sol Reinach, P., Liu, Z., Li, W. 2018; 50 (3): e451


    Sleep deficiency is a common public health problem associated with many diseases, such as obesity and cardiovascular disease. In this study, we established a sleep deprivation (SD) mouse model using a 'stick over water' method and observed the effect of sleep deficiency on ocular surface health. We found that SD decreased aqueous tear secretion; increased corneal epithelial cell defects, corneal sensitivity, and apoptosis; and induced squamous metaplasia of the corneal epithelium. These pathological changes mimic the typical features of dry eye. However, there was no obvious corneal inflammation and conjunctival goblet cell change after SD for 10 days. Meanwhile, lacrimal gland hypertrophy along with abnormal lipid metabolites, secretory proteins and free amino-acid profiles became apparent as the SD duration increased. Furthermore, the ocular surface changes induced by SD for 10 days were largely reversed after 14 days of rest. We conclude that SD compromises lacrimal system function and induces dry eye. These findings will benefit the clinical diagnosis and treatment of sleep-disorder-related ocular surface diseases.

    View details for DOI 10.1038/emm.2017.285

    View details for PubMedID 29497171

    View details for PubMedCentralID PMC5898890

  • Ectodysplasin A regulates epithelial barrier function through sonic hedgehog signalling pathway. Journal of cellular and molecular medicine Li, S., Zhou, J., Zhang, L., Li, J., Yu, J., Ning, K., Qu, Y., He, H., Chen, Y., Reinach, P. S., Liu, C. Y., Liu, Z., Li, W. 2018; 22 (1): 230–40


    Ectodysplasin A (Eda), a member of the tumour necrosis factor superfamily, plays an important role in ectodermal organ development. An EDA mutation underlies the most common of ectodermal dysplasias, that is X-linked hypohidrotic ectodermal dysplasia (XLHED) in humans. Even though it lacks a developmental function, the role of Eda during the postnatal stage remains elusive. In this study, we found tight junctional proteins ZO-1 and claudin-1 expression is largely reduced in epidermal, corneal and lung epithelia in Eda mutant Tabby mice at different postnatal ages. These declines are associated with tail ulceration, corneal pannus formation and lung infection. Furthermore, topical application of recombinant Eda protein markedly mitigated corneal barrier dysfunction. Using cultures of a human corneal epithelial cell line and Tabby mouse skin tissue explants, Eda up-regulated expression of ZO-1 and claudin-1 through activation of the sonic hedgehog signalling pathway. We conclude that EDA gene expression contributes to the maintenance of epithelial barrier function. Such insight may help efforts to identify novel strategies for improving management of XLHED disease manifestations in a clinical setting.

    View details for DOI 10.1111/jcmm.13311

    View details for PubMedID 28782908

    View details for PubMedCentralID PMC5742694

  • Ectodysplasin A protein promotes corneal epithelial cell proliferation. The Journal of biological chemistry Li, S., Zhou, J., Bu, J., Ning, K., Zhang, L., Li, J., Guo, Y., He, X., He, H., Cai, X., Chen, Y., Reinach, P. S., Liu, Z., Li, W. 2017; 292 (32): 13391–401


    The EDA gene encodes ectodysplasin A (Eda), which if mutated causes X-linked hypohidrotic ectodermal dysplasia (XLHED) disease in humans. Ocular surface changes occur in XLHED patients whereas its underlying mechanism remains elusive. In this study, we found Eda was highly expressed in meibomian glands, and it was detected in human tears but not serum. Corneal epithelial integrity was defective and the thickness was reduced in the early postnatal stage of Eda mutant Tabby mice. Corneal epithelial cell proliferation decreased and the epithelial wound healing was delayed in Tabby mice, whereas it was restored by exogenous Eda. Eda exposure promoted mouse corneal epithelial wound healing during organ culture, whereas scratch wound assay showed that it did not affect human corneal epithelial cell line migration. Epidermal growth factor receptor (EGFR), phosphorylated EGFR (p-EGFR), and phosphorylated ERK1/2 (p-ERK) were down-regulated in Tabby mice corneal epithelium. Eda treatment up-regulated the expression of Ki67, EGFR, p-EGFR, and p-ERK in human corneal epithelial cells in a dose-dependent manner. In conclusion, Eda protein can be secreted from meibomian glands and promotes corneal epithelial cell proliferation through regulation of the EGFR signaling pathway. Eda release into the tears plays an essential role in the maintenance of corneal epithelial homeostasis.

    View details for DOI 10.1074/jbc.M117.803809

    View details for PubMedID 28655773

    View details for PubMedCentralID PMC5555198