June 2022
Volume 63, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2022
Human neuritin 1: Therapeutic Strategy for Juvenile Open-Angle Glaucoma
Author Affiliations & Notes
  • Shahna Shahul Hameed
    Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, Indiana, United States
    Eugene and Marilyn Glick Eye Institute, Indiana University School of Medicine, Indianapolis, Indiana, United States
  • Ryan C.S. Miller
    Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, Indiana, United States
    Eugene and Marilyn Glick Eye Institute, Indiana University School of Medicine, Indianapolis, Indiana, United States
  • Tasneem Putliwala Sharma
    Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, Indiana, United States
    Eugene and Marilyn Glick Eye Institute, Indiana University School of Medicine, Indianapolis, Indiana, United States
  • Footnotes
    Commercial Relationships   Shahna Shahul Hameed None; Ryan Miller None; Tasneem Sharma Glaukos, Code C (Consultant/Contractor), U.S. patent application number 16/395610, Code P (Patent)
  • Footnotes
    Support  Research to prevent blindness, Knights Templar Eye Foundation
Investigative Ophthalmology & Visual Science June 2022, Vol.63, 1621 – A0444. doi:
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    • Get Citation

      Shahna Shahul Hameed, Ryan C.S. Miller, Tasneem Putliwala Sharma; Human neuritin 1: Therapeutic Strategy for Juvenile Open-Angle Glaucoma. Invest. Ophthalmol. Vis. Sci. 2022;63(7):1621 – A0444.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Juvenile open-angle glaucoma (JOAG) has early childhood disease manifestation and is associated with significant vision loss. Intraocular pressure (IOP) in these patients sometimes ranges over 40 mm Hg. JOAG has a strong genetic component and clinical management of JOAG can be quite challenging with current treatment options only limited to lowering IOP. We have previously shown that the secreted human protein neuritin 1 (NRN1) exhibits neuroprotection, regeneration and preservation of retinal ganglion cell (RGC) function after axonal injury. We propose to model JOAG by culturing human posterior eyecups within our novel ex-vivo Translaminar Autonomous System (TAS). In this system, we will overcome elevated IOP mediated RGC degeneration by over-expressing NRN1 as a therapeutic strategy.

Methods : Human donor eyes were obtained from eye banks. To recapitulate JOAG glaucomatous conditions in an ex-vivo environment, dissected human posterior cups (n=4) were cultured in the TAS model at elevated IOP conditions over 6 days with and without recombinant hNRN1. To induce translaminar pressure changes, the flow rate of the perfusion medium was adjusted and calculated using automated pumps and software. We assessed the survival of retinal ganglion cells with and without NRN1 treatment by TaqMan array analysis of apoptosis/inflammatory markers (retina). Expression of FN and COLIV was examined from the conditioned medium of both groups by Western blot analysis.

Results : We successfully maintained IOP: ICP differentials over 6 days (n=4). The RGCs degenerated faster in non-treated conditions compared to NRN1 treated eyes. In contrast to the controls, the treated group significantly decreased expression of FN and COLIV (p<0.05, n=4). We observed downregulated expression of GFAP (p<0.001, n=4), BAX and TLR4 expression (p<0.05, n=4) after NRN1 treatment.

Conclusions : Our data identified that NRN1 treatment promotes RGC survival under pathological conditions of glaucoma. This study suggests that hNRN1 could be utilized as a potential therapeutic to save RGC and a plausible treatment option for JOAG.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.

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