# Molecular Mechanism of αAN101D-Transgene-Induced Age-Related Cataract

> **NIH NIH R01** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2021 · $382,927

## Abstract

The proposal has the overall goal to determine the molecular mechanisms of an age-related cortical cataract
development. Cataracts are principally a lens structural proteins' (crystallins) aggregation and subsequent
precipitation disease that are inducible by genetic mutations, and occurs due to aging. During cataract
development, the increased sizes of aggregated and cross-linked crystallin multimers become so large that they
finally become water insoluble and cause lens opacity. Several post-translational modifications (PTMs) of
crystallins are known to cause age-related cataracts, and the deamidation of crystallins (the most abundant
among post-translational modifications) is considered as a major cataract-causative factor. In spite of voluminous
literature on in vitro studies of effects of crystallins' deamidation leading to cataract-development, no clear
molecular mechanism has emerged that could implicate the deamidation-induced link of the in vitro effects to in
vivo changes. Therefore, the PI's-generated unique αA-N101D mouse model, where asparagine 101 is
deamidated to aspartic acid, provides an opportunity to directly link the in vitro studies to in vivo changes in
phenotypic and crystallins' properties to the cortical cataract development. The model would provide information
about the molecular mechanism of age-related cataract development. Based on our extensive results, we have
hypothesized that the cataract in αAN101D mouse model is caused by the altered crystallin properties, cellular
defects and synergistically increased deposit of αAN101D with membrane, resulting in membrane disruption and
ionic imbalance. We plan to test the above hypothesis by seeking answers the following three questions using
the above mouse model: (A) Aim 1: Does deamidated αAN101D causes temporal alterations in crystallin-
crystallin interactions leading to aggregation among crystallins and their insolubilization in vivo? (B)
Aim 2: What are the temporal sequence of lens phenotypes that cause cellular defects during the cortical
cataract development? (C) Aim 3: Does temporal increase in binding of deamidated αAN101D to
membrane leads to membrane disorganization and intracellular ionic imbalance? The results will be of
significant therapeutic value to delay the development and progression of age-related cataracts.

## Key facts

- **NIH application ID:** 10133671
- **Project number:** 5R01EY031303-02
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** Om Prakash Srivastava
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $382,927
- **Award type:** 5
- **Project period:** 2020-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10133671

## Citation

> US National Institutes of Health, RePORTER application 10133671, Molecular Mechanism of αAN101D-Transgene-Induced Age-Related Cataract (5R01EY031303-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10133671. Licensed CC0.

---

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