Date of Defense

4-17-2018

Date of Graduation

4-2018

Department

Biological Sciences

First Advisor

Cindy Linn

Second Advisor

David Paul

Third Advisor

Cynthia Cooley-Themm

Abstract

Biomarkers are measurable substances in an organism that are indicative of some phenomenon. Examples of biomarkers in clinical settings are body temperature and blood pressure. Body temperature is indicative of a fever while blood pressure can be used to monitor someone’s risk of a stroke. Previous studies have investigated the possibility of there being a potential biomarker for glaucoma. One possible biomarker identified is growth differentiation factor 15 or GDF15. These studies prompted a study in our lab using a rat glaucoma model. The objective of this study was to show there is a biomarker present for the neurodegenerative disease, glaucoma. To mimic the effects of glaucoma, adult healthy rats were anesthetized using a KAX solution, and NaCl was injected into the episcleral veins of experimental eyes to induce scarring in the trabecular meshwork and induce glaucoma-like conditions. In each animal, only one eye was subjected to this procedure. The other eye was left untreated and acted as an internal control. After a specific period of time, the rats were euthanized, and their retinas and aqueous humor were removed. The retinas and aqueous humor from untreated control eyes and from experimental eyes were quantified for GDF15 protein levels using an enzyme-linked immunosorbent assay (ELISA). After quantifying protein expression in both sets of eyes, a separate experiment was done by adding neuroprotective to the experimental eye to see if it had any effect on the GDF15 expression. Previous studies have found that activation of alpha 7 nicotinic acetylcholine receptors, α7nAChRs, in the eye reduces retinal ganglion cell death associated with glaucoma. The neuroprotective used in this study was PNU-282987. PNU-282987 was added to untreated and experimental eyes to determine if its effect on GDF15 protein expression. It was found that there was an increase in GDF15 expression after injection with hypertonic saline. This increase was most prevalent at 3 days and 7 days post operation. This increase means that GDF15 is a potential biomarker for glaucoma. The results from the neuroprotective experiment yielded promising results. There was no significant difference between the eyes treated with PNU-282987, the eyes not treated with PNU-282987, and the control eyes. This result suggests that the neuroprotection worked in preventing the expression of GDF15. The results also showed possible cross over between the eyes since the untreated eyes that had been induced with glaucoma-like conditions also showed no significant difference. To know for sure more experiments need to be done. An early glaucoma marker such as GDF15 levels could help lead to a faster diagnosis in those affected and help us gain a better understanding of the disease itself.

Access Setting

Honors Thesis-Open Access

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