# Sex Hormones and Keratoconus

> **NIH NIH R01** · UNIVERSITY OF NORTH TEXAS HLTH SCI CTR · 2020 · $365,000

## Abstract

PROJECT SUMMARY/ABSTRACT
Keratoconus (KC) is the most common corneal dystrophy with clinical findings that include discomfort, visual
disturbance, a negative impact on daily living (reading, driving, computer use and so on), and possible
blindness if left untreated. KC affects approximately 1:400 people worldwide, including both males and
females. During KC progression, the cornea slowly changes from its normal curved shape to a more conical
shape, corneal thinning, and scarring, leading to vision distortion. Clinically, there are rather limited treatment
options for KC patients, such as corneal transplantation and collagen cross-linking. Unfortunately, both corneal
transplantation and collagen cross linking have their own limitations, primarily because the etiology of KC is
largely unknown. As a result, we have yet to see the first animal model that mirrors KC dystrophy. As such,
there is an urgent need to identify novel pathways and develop targeted treatment modalities. In 2012, we
were the first to establish a novel in vitro 3-dimensional (3D) culture system consisting of human keratoconus
cells (HKCs), which allows us to investigate and identify cellular mechanisms that are driving the disease.
Since then, we have shown that our model can mirror the KC defects seen in vivo, including scarring, matrix
thinning, and oxidative stress. Our preliminary data shows that sex hormones are a key KC mediator. Sex
hormones were identically regulated both in vitro and in vivo based on results from three different systems: 3D
in vitro model, human tears, and human saliva. Using these non-invasive systems we have begun unravelling
an intriguing mechanism about KC onset and progression. We hypothesize that sex hormones imbalance
initiate a cascade of downstream signals that collectively are responsible for the onset of KC. Naturally, we
would like to pursue these findings and determine the role of sex hormones in KC. Excitingly, we are in a
unique position where we can determine their role in vivo using human tears and saliva samples from KC and
Healthy donors. We can then link our in vitro and in vivo findings and determine the mechanism of KC onset. In
order to strengthen our proposal and ensure feasibility, we have put together a team of national and
international experts in KC, both clinicians and basic scientists. We also have the support and collaboration of
the National Keratoconus Foundation (NKCF). Successful completion of the proposed studies could ultimately
lead to the development of novel treatments for KC.
Relevance to Public Health – KC is a major clinical problem resulting in visual impairment worldwide. The lack
of animal models require for us to develop novel, noninvasive tools for the treatment of KC. Ultimately,
noninvasive therapeutics may lead to early arrest of the KC development. The proposed work is translational,
clinically relevant, and in line with NEI’s goals and research priorities to understand KC and develop novel
treatment o...

## Key facts

- **NIH application ID:** 9915927
- **Project number:** 7R01EY028888-03
- **Recipient organization:** UNIVERSITY OF NORTH TEXAS HLTH SCI CTR
- **Principal Investigator:** Dimitrios Karamichos
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $365,000
- **Award type:** 7
- **Project period:** 2018-05-01 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9915927

## Citation

> US National Institutes of Health, RePORTER application 9915927, Sex Hormones and Keratoconus (7R01EY028888-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9915927. Licensed CC0.

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