# Discovery Approach to Ocular Hypertension

> **NIH NIH R01** · TUFTS MEDICAL CENTER · 2020 · $592,931

## Abstract

7. PROJECT SUMMARY/ABSTRACT
This application proposes an innovative and powerful multidimensional approach to discover novel genes and
pathways that may serve as therapeutic targets for ocular hypertension (OH). It focuses on a secondary form
of OH caused by treatment with glucocorticoids (GCs). GCs are used to treat a wide variety of diseases,
including many eye diseases. A drawback however, is that use of GCs in the eye results in a potentially sight
threatening increase in intraocular pressure (IOP) in up to half of patients. This is genetically determined, thus,
steroid-induced OH (SIOH) can be investigated using genetic approaches that requires no a prior biological
knowledge. The pathophysiology of SIOH bears similarities to a much more common form of OH that leads to
Primary Open Angle Glaucoma (POAG), but SIOH also has unique features as well. Importantly, SIOH has the
advantages of a much shorter observation period and much larger effect sizes than POAG. Therefore, the
study of SIOH could make it possible to discover pathways that would not have been revealed any other way.
In addition, sensitivity to SIOH is important to study in its own right, as it limits the usefulness of a very effective
class of anti-inflammatory drugs and genetic variants discovered might be used predictively to make steroid
use safer for patients. In work conducted over a number of years, the multi-PIs have demonstrated the power
and effectiveness of their approach for discovery of novel genes and pathways, several of which represent
promising new therapeutic targets. Now ready for a full-fledged discovery effort, they have partnered with
leaders of a large clinical practice to utilize a unique cohort of demographically homogenous Fuch's endothelial
corneal dystrophy (FECD) patients that received corneal transplants, all treated in a highly uniform way with
GCs following surgery, with careful pre-surgical characterization and post-surgical IOP follow-up. Thus this
cohort is already fully phenotyped. Moreover, many patients have been enrolled in an NIH-funded genetic
study of FECD, meaning many DNA samples have already been collected. In the planned study, the maximum
change in IOP following GC treatment (ΔIOP) will serve as the quantitative trait, as in previous studies from this
team. DNA sequencing will be added to microarray-based genotyping to enhance opportunity for discovery of
rare genetic variants. At the same time the research team will continue follow-up, adding new leads as they
arise. The proposed Specific Aims are as follows: 1) complete collection of DNA; 2) perform hybrid genomic
analysis, combining microarray genotyping with whole genome sequencing; 3) identify genomic variants
statistical associated with the quantitative trait; 4) investigate functional significance of the top quantitative trait
loci and associated genes. Application of the multidimensional approach outlined here is predicted to have high
impact, leading to the advancement of pre...

## Key facts

- **NIH application ID:** 9921393
- **Project number:** 5R01EY027315-04
- **Recipient organization:** TUFTS MEDICAL CENTER
- **Principal Investigator:** M Elizabeth Fini
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $592,931
- **Award type:** 5
- **Project period:** 2017-08-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9921393

## Citation

> US National Institutes of Health, RePORTER application 9921393, Discovery Approach to Ocular Hypertension (5R01EY027315-04). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/9921393. Licensed CC0.

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