Abstract
Purpose :
Glaucoma is one of the leading causes of blindness. Elevated intraocular pressure (IOP) is the major risk factor of glaucoma. The TGFβ2-induced ocular hypertension mouse model has been widely used to study the pathological changes in the glaucomatous trabecular meshwork (TM). Since most of the published studied used old and female mice with 2.5X107 PFU Ad5-CMV-TGFβ2 virus, in this study, we determined if age and sex affect IOP in this well-established ocular hypertensive mouse model.
Methods :
We used young (3 month, n=14) and old (5 month, n=10) male C57BL/6J mice. One eye was injected intravitreally with Adenovirus expressing human TGFβ2 (Ad5-CMV-TGFβ2) at 2.5X107 PFU or 5.0X107 PFU and the fellow eye with the same amount of Ad5-CMV-GFP adenovirus as a control. IOP was measured up to 11 weeks. At the end of the study, the mice were euthanized and the eyes were used for ELISA, qPCR and immunofluorescent staining.
Results :
We observed a significant IOP elevation in both 3 and 5 month old male mouse eyes injected with 5.0X107 PFU Ad5-CMV-TGFβ2. However, 5 month old male mice respond early with higher IOP compared to 3 month old male mice. In contrast, no IOP elevation was observed in either groups of mouse eyes treated with 2.5X107 PFU Ad5-CMV-TGFβ2. ELISA and qPCR showed a robust expression of human TGFβ2 expression in the aqueous humor in Ad5-CMV-TGFβ2 injected eyes. Similarly, immunofluorescent staining showed elevated levels of human TGFβ2 and fibronectin in the TM region in Ad5-CMV-TGFβ2 injected eyes.
Conclusions :
Male C57BL/6J mice requires high dose of adenoviruses to develop IOP elevation compared to female mice. Also, older male mice are more sensitive to the Ad5-CMV-TGFβ2 virus.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.