ROLE OF MACROPHAGES IN DIABETES-ASSOCIATED OCULAR SURFACE INJURY

Abstract

Diabetes mellitus is a major global health concern characterized by impaired carbohydrate metabolism and chronic hyperglycemia. Approximately 589 million individuals worldwide are currently affected, with projections reaching nearly 853 million by 2050. In the United States alone, around 51 million people live with diabetes, with a significant proportion remaining prediabetic. Poor glycemic control leads to both microvascular and macrovascular complications. Diabetes causes multifactorial ocular complications like diabetic retinopathy, cataracts, glaucoma, diabetic papillopathy, and ocular surface damage. These complications substantially elevate the risk of vision impairment and negatively impact quality of life. The ocular surface, including the cornea, conjunctiva, eyelids, limbus, tear film, and associated glands, acts as the eye’s first barrier against environmental insults. Hyperglycemia disrupts this system by impairing tear production, increasing osmolarity, reducing epithelial cell regeneration, and promoting apoptosis, thus enhancing susceptibility to infection. In parallel, diabetes induces immune dysfunction, impairing key innate immune cells like macrophages, neutrophils, dendritic cells, and NK cells. Despite their critical role, the effects of diabetes on macrophages within the lacrimal functional unit have not been systematically studied. To address this, we established a method for detecting and localizing macrophages in the cornea, conjunctiva, and lacrimal glands using markers such as CD11b, F4/80, and CD206. We then investigated the effect of hyperglycemia on macrophages within the lacrimal functional unit utilizing a mouse model of streptozotocin-induced diabetes. Our data demonstrate that short-term hyperglycemia alters the macrophage population and activation, leading to compromised immune defense. Our findings emphasize that even short-term poor glycemic control induces tissue-specific damage within the lacrimal functional unit. These results highlight the necessity for glycemic control to protect immune cell function and maintain ocular surface health, ultimately reducing the risk of diabetes-associated vision complications.