Skip to main content
. Author manuscript; available in PMC: 2023 Aug 1.
Published in final edited form as: Trends Mol Med. 2022 May 29;28(8):644–661. doi: 10.1016/j.molmed.2022.05.007

Figure 5. In vivo models of chronic ocular diseases and their calpain-associated pathologies.

Figure 5.

Calpains are involved in common chronic ocular diseases: (A) cataract, (B) diabetic retinopathy, and (C) glaucoma. A congenital cataract model using New Zealand Romney sheep displayed inherited cataract. Cataracts caused by environmental oxidative stress can be modeled by selenite injection into rats. In both cataract models, CAPN1, CAPN2, and a lens-specific splice variant of CAPN3 (Lp82) were increasingly activated, which causes lens opacification. The diabetic retinopathy mouse model is induced by streptozotocin (STZ) injection, which severely damages pancreatic beta cells to induce hyperglycemia. It demonstrated increased activation of CAPN5 and CAPN10 as well as increased expression of CAPN1. As a result, oxidative stress and apoptotic pathways were activated and led to retinal ganglion cell (RGC) degeneration. Glaucoma murine models employed optic nerve injury to induce RGC death by activating CAPN1 and its downstream apoptotic pathways. A multitude of calpain inhibitors were shown to ameliorate the disease phenotypes in these in vivo models. Additionally, knock-out Lp82 mice and knock-out CAPN1 mice exhibited decreased disease progression.