# Testing the role of Glucose deprivation during secondary cone death in Retinitis Pigmentosa

> **NIH NIH R21** · UNIV OF MASSACHUSETTS MED SCH WORCESTER · 2020 · $209,375

## Abstract

PI: Claudio Punzo
Project Summary
The inter-neuronal relationship between rod and cone photoreceptors in human and mouse is such that rod
death always leads to cone death; however, loss of cones has no effect on rods. This phenomenon plays an
important role in the inherited retinal degenerative disease retinitis pigmentosa, as most disease-causing
alleles identified encode for genes that are exclusively expressed in rods. Since cones are essential for human
vision, it is their loss that leads to blindness. We have recently proposed that cone death is a cell autonomous
event caused by reduced nutrient uptake, in particular glucose, and showed that cell autonomous activation of
the kinase mammalian target of rapamycin complex 1 (mTORC1), by deletion of its negative regulator the
tuberous sclerosis complex protein 1 (TSC1), significantly prolongs cone survival. Since our initial findings
others have also supported the notion that secondary cone death in retinitis pigmentosa is manly caused by a
shortage of glucose in cones. Our cell autonomous activation of mTORC1 in cones promoted cone survival by
improving the following 3 glucose related processes: uptake, retention and metabolism. In this grant we want
to test to which extent each of these 3 processes contributes to cone survival. We have identified 3 genes,
through a rational analysis of our data, each representing one of these 3 processes. Here we propose to test
how much each gene contributes to cone survival by rAAV mediated gene transfer to cones. We will test the
cone survival effect mediated by each gene individually and in combination of two genes at the same time. To
ensure that our approach is mutation independent we will carry out our experiments in two mouse models of
retinitis pigmentosa. Accomplishment of the proposed research will lay the foundation for the design of a
rational therapeutic approach to extend vision in humans with retinitis pigmentosa.

## Key facts

- **NIH application ID:** 9919561
- **Project number:** 5R21EY030166-02
- **Recipient organization:** UNIV OF MASSACHUSETTS MED SCH WORCESTER
- **Principal Investigator:** Claudio Punzo
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $209,375
- **Award type:** 5
- **Project period:** 2019-05-01 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9919561

## Citation

> US National Institutes of Health, RePORTER application 9919561, Testing the role of Glucose deprivation during secondary cone death in Retinitis Pigmentosa (5R21EY030166-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9919561. Licensed CC0.

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