# Non-hydrolysable analogs of retinal chromophore; potential new therapeutics to prevent retinal degeneration

> **NIH NIH R01** · CASE WESTERN RESERVE UNIVERSITY · 2020 · $356,625

## Abstract

   
DESCRIPTION (provided by applicant): An insufficient supply of visual chromophore due to dysfunction of key proteins involved in its regeneration has devastating effects on rod-mediated vision, and comprises a leading cause of irreversible blindness in humans. Early signs of such blinding diseases are delayed rod cell-mediated dark adaptation and difficulty with night vision. The decline in recovery of visual sensitivity is likely caused by inadequate Rho regeneration with accumulation of chromophore-free opsin that constitutively activates the signaling cascade and accelerates retinal degeneration. Although such free opsin activity can be reduced by exogenous retinal chromophore, this fails to prevent the buildup of toxic retinoid photo-products when their clearance is defective. Thus, an alternative therapeutic approach is urgently needed for combating vision loss under such conditions. Here we propose to investigate the effects of new visual pigments, retinyl-opsins regenerated with novel chromophore analogs, retinyl chlorides on retina physiology in context of potential therapeutic strategy to protect retinal healh in retinal degenerative diseases associated with compromised Rho regeneration. First, we will study the biochemical and functional properties of different retinyl chloride isomers in vitro (Aim
1), and then test the effects of selected retinyl chlorides in both Abca4-/-Rdh8-/- mice, a model of early onset human Stargardt disease and in Lrat-/- mice, a model of Leber congenital amaurosis (LCA) (Aim 2). Finally, we will assess the capability of the RBP4 carrier to increase the ocular delivery of these compounds, and thereby alleviate progressive retinal degeneration in these mouse models (Aim 3).

## Key facts

- **NIH application ID:** 9899990
- **Project number:** 5R01EY025214-05
- **Recipient organization:** CASE WESTERN RESERVE UNIVERSITY
- **Principal Investigator:** Beata Jastrzebska
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $356,625
- **Award type:** 5
- **Project period:** 2016-04-01 → 2021-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9899990

## Citation

> US National Institutes of Health, RePORTER application 9899990, Non-hydrolysable analogs of retinal chromophore; potential new therapeutics to prevent retinal degeneration (5R01EY025214-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9899990. Licensed CC0.

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