# Novel Mechanisms of Subretinal Fibrosis in Age-related Macular Degeneration

> **NIH NIH R01** · DOHENY EYE INSTITUTE · 2020 · $391,561

## Abstract

Project Abstract
Age-related macular degeneration (AMD) remains a leading cause of loss-of-vision that necessitates
mechanistic studies of disease and the development of new therapeutics. Early AMD progresses to later,
blinding forms following one of two divergent pathways: i) Atrophic AMD is associated with degeneration and
death of retinal pigment epithelium (RPE); and ii) choroidal neovascularization (CNV) is associated with growth
of new vessels under the retina. While there are treatments for CNV using anti-angiogenic drugs, there are no
effective treatments for subretinal fibrosis (SRF). SRF is a complication of both end-stage and treated CNV
that results in severe to profound visual impairment. To address this complication, our team invented a novel
αB-crystallin peptide nanoparticle (αBC-ELP) that markedly inhibits the progression of SRF. Elastin-like
polypeptides (ELPs) are high molecular weight biocompatible biopolymers derived from human tropoelastin
that retain a biologically-active fragment of the αB-crystallin protein near the retina for extended periods, thus
enabling their therapeutic efficacy. As supported by our preliminary data, we hypothesize that αBC-ELP will
prevent the progression of SRF compared to controls. We further hypothesize that the inhibitory effect of
(αBC-ELP) on SRF decreases the generation of fibrosis-promoting, senescent cells and improves the
regulation of mitochondrial metabolism by promoting oxidative phosphorylation. These hypotheses will be
tested using the following Specific Aims: Aim #1. Characterize ocular pharmacokinetics of intravitreal αBC-
ELP in mouse and rabbit eyes. Aim #2. Characterize SRF and determine effect and time course of αBC-ELP
in laser model of CNV. Aim #3. Establish the mechanistic role of senescence cells in progression of SRF and
the mechanism of its inhibition by αBC-ELP. Aim #4. Establish the mechanistic role of mitochondrial
bioenergetics and mitochondrial SMAD4 in SRF and the mechanism of its inhibition by αBC-ELP.

## Key facts

- **NIH application ID:** 9972646
- **Project number:** 1R01EY030141-01A1
- **Recipient organization:** DOHENY EYE INSTITUTE
- **Principal Investigator:** RAM KANNAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $391,561
- **Award type:** 1
- **Project period:** 2020-05-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9972646

## Citation

> US National Institutes of Health, RePORTER application 9972646, Novel Mechanisms of Subretinal Fibrosis in Age-related Macular Degeneration (1R01EY030141-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9972646. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*