Comparative Ocular Parameters of the ESR1 Conditional Knockout Mouse Open Access

Abstract

Importance: Glaucoma is the leading cause of irreversible blindness worldwide, and females represent nearly 60% of the affected population. Menopause and estrogen signaling dysfunction is a sex-specific risk factor, though the estrogen signaling mechanism remains unclear. Establishing a successful estrogen receptor 1 (ESR1) conditional knockout mouse model will be instrumental in studying the local signaling of estrogen and how therapeutics can be developed to mitigate these sex-specific risk factors and treat glaucoma.

 

Objective: To validate that there are no baseline differences in ocular measurements between the different mice strains (C57, ESR1cKO, and ESR1floxed) and assess whether the conditional knockout (ESR1cKO) strain can be used as a potential mouse model to study possible neuroprotective effects of ESR1 in future studies.

Methods: C57, ESR1cKO, and ESR1floxed (n = 25-28) underwent 2 weeks of in vivo ocular measurements to assess intraocular pressure (IOP), visual function (OMR), retinal structure (OCT), and retinal function (ERG). Afterward, histological (H&E) images were also obtained from a subset of animals (n = 23) to perform ocular dimension analyses.

Results: No strain differences were found in most ocular parameters including spatial frequency, retinal structure, and ocular dimensions. We found the C57 mean IOP to be 12.9% and 11.2% higher than the ESR1floxed and ESR1cKO strains, respectively. From the ERGs, we found the ESR1cKO strain to exhibit the fastest scotopic c-wave response and the strongest photopic b-wave response while all other retinal responses remained the same across strains.

Conclusion: The ESR1cKO strain is a promising mouse model to study possible neuroprotective effects of ESR1, such as in RGC injury experiments, which could inform future therapeutic avenues for glaucoma.

Table of Contents

1. Introduction…………………………………………………………………………………...................1

2. Methods………………………………………………………………………………….........................4

2.1. Animals…………………………………………………………………………….............................4

2.2. Intraocular pressure…………………………………………………………................................5

2.3. Visual function……………………………………………………………………...........................6

2.4. Retinal structure…………………………………………………………………............................7

2.5. Retinal function……………………………………………………………………..........................8

2.6. Histology…………………………………………………………………………..............................9

2.7. Statistical analysis……………………………………………………………..........…..................10

3. Results…………………………………………………………………………………..........................11

3.1. Intraocular pressure……………………………………………………………….........................11

3.2. Visual function……………………………………………………………………..........................12

3.3. Retinal structure…………………………………………………………….….............................13

3.4. Retinal function…………………………………………………………………............................14

3.5. Ocular dimensions……………………………………………………………..............................18

4. Discussion………………………………………………………………………………….....................20

5. Conclusion…………………………………………………………………………………....................22

6. References………………………………………………………………………………….....................23

Figures and Graphs

Figure 1. Research design schematic ..................................................................................5

Figure 2. IOP results .......................................................................................................12

Figure 3. Visual function results ......................................................................................12

Figure 4. Retinal structure results....................................................................................13

Figure 5. Retinal function: Scotopic ERG results................................................................15

Figure 6. Retinal function: Photopic ERG results...............................................................17

Figure 7. Retinal function: Flicker ERG results ..................................................................18

Figure 8. H&E staining of a mouse eye tissue annotating ocular dimensions analyzed..........18

Figure 9. Ocular dimensions results..................................................................................19 

About this Honors Thesis

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School	Emory College
Department	Neuroscience and Behavioral Biology
Degree	B.S.
Submission	Honors Thesis
Language	English
Research Field	Engineering, Biomedical Biology, Neuroscience Health Sciences, Ophthalmology
Keyword	Glaucoma Estrogen Receptor 1 Estrogen
Committee Chair / Thesis Advisor	Feola, Andrew, Emory University
Committee Members	Pardue, Machelle , Emory University Devineni, Anita , Emory University

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	Sample Sizes (Sample sizes used in the study for each type of ocular measurement)	2025-03-26 22:17:33 -0400	Press to Select an action Download