Investigating the long-term effect of latanoprost treatment on a partially open-angle mouse model of glaucoma

Abstract

Purpose : Glaucoma is a blinding disease that is primarily divided into two major subgroups: primary open-angle glaucoma and angle-closure glaucoma. Angle-closure glaucoma is further subdivided into complete and partial angle-closure glaucoma. The purpose of this study is to test the effectiveness of latanoprost (LTP) treatment on a partially open-angle mouse model (AP-2β TMR-KO) and its ability to facilitate prolonged reduction of intraocular pressure (IOP) and prevent retinal ganglion cell death (RGCs).

Methods : The AP-2β TMR-KO or MgpCre^+/-;tfap2b^-/lox mice, as well as control littermates, were developed by breeding male MgpCre^+/-;tfap2b^+/- with female tfap2b^lox/lox mice. An equal number of mutant and wildtype littermates were treated with 0.005% LTP (10μl in each eye) for 60 consecutive days to test for the long-term effect of LTP in our mouse model. IOP measurements were taken every three days. Upon the end of the treatment period, the mice were euthanized, and their eyes were enucleated, fixed, sectioned, and stained for retinal ganglion cells using Brn3a (n=3).

Results : The IOP of the AP-2β TMR KO mice (21.54mmHg±0.86) was significantly elevated (n =10 eyes, P < 0.0001) when compared with control mice (10.32±0.42). During the time of treatment, the IOP measurements of control mice were normal across all three cohorts (10.72mmHg±0.67, n=14). In contrast, the mutant mice showed a consistent downward pattern of the baseline IOP (23.17mmHg±0.72) with a significant reduction in IOP at 35 days of treatment across all cohorts (17.71mmHg±0.51, n =16, P < 0.0001). The staining of Brn3a revealed a decrease in the RGC population in treated mutant eyes when compared to the treated control eyes.

Conclusions : Our findings show that long-term LTP treatment significantly reduces the baseline IOP in our glaucoma mouse model. While we observed a reduction in baseline IOP, it was not sufficient to protect the loss of RGCs in the mutant. The reduction in IOP upon LTP treatment in the mutant animals show effective functioning of the uveoscleral outflow pathway. Based on our current study, we believe that continuous exposure to latanoprost over an extended period may allow for the reduction of baseline IOP and prevent glaucomatous features in AP-2β TMR-KO. This model can be used to test for other candidate IOP lowering drugs in future studies.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.