# Sex Dependent Regulation of Retinol Degeneration

> **NIH NIH R01** · TUFTS MEDICAL CENTER · 2022 · $186,262

## Abstract

Summary:
 Retinal detachment (RD), caused by injury or retinal disorders (e.g. age-related macular degeneration
and diabetic retinopathy), is a leading cause of retinal degeneration and vision loss. In patients with sustained
RD, progressive visual decline due to photoreceptor cell death is common and leads to a significant decrease
in visual acuity. However, the underlying biological processes controlling photoreceptor cell death in this
context are not well understood and currently no treatments exist, aside from surgery to reattach the retina.
Cell death during RD is thought to be caused by the physical separation between the photoreceptors and their
primary source of oxygen and nutrients resulting in severe ischemia and metabolic distress. Our preliminary
evidence has demonstrated that male mice with a RD have a significant increase in photoreceptor cell death
compared to their female counterparts. Moreover, we have identified estrogen as a key modulator of
photoreceptor susceptibility to RD injury. Importantly, in many brain degenerative diseases, estrogen exerts its
neuroprotective actions by improving mitochondrial function and reducing oxidative damage.
 The goal of this study therefore is to test the hypothesis that females are protected from RD-induced
retinal degeneration through the actions of estrogen-dependent normalization and/or rescue of photoreceptor
metabolic dysfunction. We will utilize a well-defined mouse model of RD, in which a subretinal injection of
sodium hyaluronate is used to create a detachment. The mouse RD model will allow us to take advantage of
well-established genetic manipulation platforms in mice in a controlled setting. In order to characterize the role
of sex and the estrogen signaling system in photoreceptor cell death we will: 1) Define how estrogen signaling
is modulated in vivo using genetic models and gonadectomy to precisely delineate the signaling pathways and
metabolic processes involved in estrogen-dependent rescue of photoreceptor degeneration; 2) Elucidate the
role of estrogen in alleviating mitochondrial stress and oxidative damage in photoreceptors in response to RD;
3) Delineate the specific metabolic pathways, key metabolites and mitochondrial functions involved in the sex
dependent regulation of cell death in RD. It is our belief that this study will yield insights into the role of
estrogen in retinal neuroprotection and provide new sex-specific therapeutic targets and or treatment
modalities for the management of sight-threatening diseases such as RD.

## Key facts

- **NIH application ID:** 10925876
- **Project number:** 7R01EY029269-05
- **Recipient organization:** TUFTS MEDICAL CENTER
- **Principal Investigator:** Gopalan Gnanaguru
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $186,262
- **Award type:** 7
- **Project period:** 2019-04-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10925876

## Citation

> US National Institutes of Health, RePORTER application 10925876, Sex Dependent Regulation of Retinol Degeneration (7R01EY029269-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10925876. Licensed CC0.

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