Ocular surface changes in mice with Streptozotocin-induced diabetes and diabetic polyneuropathy

Abstract

Purpose : Diabetes mellitus (DM) is a leading risk factor for corneal neuropathy and dry eye disease (DED). Another common consequence of DM is diabetic peripheral polyneuropathy (DPN). Both complications affect around 50% of the DM patients but the relationship between DM, DED and DPN remains unclear.

Methods : In mice with early onset of PN after streptozotocin (STZ)-induced diabetes (DPN) morphological changes of the sciatic nerve, dorsal root and trigeminal ganglia were compared with changes in the ocular surface, including tear proteomic and respective changes in the gene expressions and morphological alterations in the eye tissues involved in tear production.

Results : The lacrimal gland, conjunctival goblet cells and cornea showed morphological changes along with alterations in tear proteins without any obvious signs of ocular surface inflammation. The tear proteomic, also showed significant changes compared to control mice. In the trigeminal ganglia like in the dorsal root ganglia neuronal cells showed swollen mitochondria and, in the latter, there was a significant increase of NADPH oxidases and MMP9 suggestive of oxidative and neuronal stress. In the dorsal root ganglia and the sciatic nerve, there was an upregulation of a number of pro-inflammatory cytokines and pain-mediating chemokines.

Conclusions : The early ocular changes in DM mice only affect the lacrimal gland, reflected in the tear film composition. Due to the high protein concentration in tear fluid in humans, proteomic analysis in addition to noninvasive investigation of goblet cells and cornea can serve as a tool for the early diagnosis of DPN, DED in clinical practice. Early treatment could delay or even prevent the ocular complications of DM such as DED and PN.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.