# Role of Tgf-beta-signaling in corneal development and diseases

> **NIH NIH R21** · TRUSTEES OF INDIANA UNIVERSITY · 2020 · $231,024

## Abstract

PROJECT SUMMARY/ABSTRACT
Transforming growth factor-beta (TGF-β) is one of the most important growth factors involved in
morphogenesis of ocular anterior segment tissues including corneal stroma, a transparent tissue layer
responsible for acquiring normal vision. We examined the hypothesis that conditional ablation of Tgfbr2-
mediated signaling pathway in keratocytes can perturb postnatal corneal development and homeostasis. We
generated a novel Tgfbr2 keratocyte knockout mice, Tgfbr2Kera-ko. These mice display a severe corneal stromal
thinning phenotype resembling keratoconus (KTCN) in humans, a progressive eye disease in which the
normally round cornea thins and begins to bulge into a cone-like shape causing distorted vision. We
hypothesize that the Tgfbr2 signaling (including Smad-dependent and/or Smad-independent) in
keratocytes is indispensable for corneal morphogenesis and homeostasis. Tgfbr2Kera-ko mouse strain is a
potential model to elucidate the molecular mechanism of TGF-β signaling pathway and its downstream
target(s) in keratocytes for corneal development and homeostasis. To our knowledge, this mouse strain may
be the first genetic-defined animal model for human KC research and therapy. We propose two specific aims to
achieve these goals.
Specific Aim 1: To elucidate the role of Tgfbr2-mediated signaling in mesenchymal keratocytes during
corneal development and homeostasis.
Specific Aim 2: To figure out the Smad-dependent or non-Smad pathway through which Tgfbr2 signaling
takes place in the keratocyte to regulate corneal development and homeostasis.
Impact: Completion of these proposed aims in two years will provide groundbreaking knowledge regarding the
critical roles of TGF-β signaling in mesenchymal keratocytes during corneal development and homeostasis-
serving as the basis for the long term goal of improving eye care and related ocular diseases like corneal
ectasia (keratoconus). On an even greater scale, the information gained from the cornea can be harnessed in
other tissue systems where mesenchymal TGF-β signaling is crucial for development, homeostasis, and
wound healing.

## Key facts

- **NIH application ID:** 9873328
- **Project number:** 1R21EY031051-01
- **Recipient organization:** TRUSTEES OF INDIANA UNIVERSITY
- **Principal Investigator:** CHIA-YANG LIU
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $231,024
- **Award type:** 1
- **Project period:** 2020-09-30 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9873328

## Citation

> US National Institutes of Health, RePORTER application 9873328, Role of Tgf-beta-signaling in corneal development and diseases (1R21EY031051-01). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9873328. Licensed CC0.

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