Ocular surface complications in diabetes: The interrelationship between insulin and enkephalin

Elevated Opioid Growth Factor Alters the Limbus in Type 1 Diabetic Rats

“…These data support the hypothesis that the corneal surface dysregulation in diabetes could be a result of dysregulation of the OGF-OGFr axis in the limbus that is partially insulin independent. All of the mechanisms contributing to the altered limbal morphology in the diabetic rat are not known, but may include systemic inflammation caused by diabetes reducing cell replication, as well as deficiencies in insulin protection [29]. Dry eye and abnormal corneal surface sensitivity are still apparent in T1D rats that are euglycemic with insulin minipumps [29].…”

“…All of the mechanisms contributing to the altered limbal morphology in the diabetic rat are not known, but may include systemic inflammation caused by diabetes reducing cell replication, as well as deficiencies in insulin protection [29]. Dry eye and abnormal corneal surface sensitivity are still apparent in T1D rats that are euglycemic with insulin minipumps [29]. However, corneal epithelial wound healing abnormalities in T1D rats that involve cell replication do appear to be responsive to insulin in that rates of wound closure are comparable to those of normal rats [29].…”

“…Dry eye and abnormal corneal surface sensitivity are still apparent in T1D rats that are euglycemic with insulin minipumps [29]. However, corneal epithelial wound healing abnormalities in T1D rats that involve cell replication do appear to be responsive to insulin in that rates of wound closure are comparable to those of normal rats [29]. Collectively these data suggest that the OGF-OGFr axis impacts corneal surface homeostasis in diabetes in a manner that is at least partially insulin independent and that a better understanding of the role of the limbal OGF-OGFr axis in ocular surface complications in diabetes could be informative regarding the pathophysiology of T1D complications and lead to improved therapies.…”

The Role of Insulin-like Growth Factor (IGF) System in the Corneal Epithelium Homeostasis—From Limbal Epithelial Stem Cells to Therapeutic Applications

“…Several studies reported ocular surface abnormalities in patients with diabetes, such as reduced tear breakup time, lower tears secretion, and increased level of inflammatory markers: NPY, STAT-5 ICAM-1, and TNF-α [ 53 , 54 , 55 ]. Clinically, diabetic ocular surface complications include reduced corneal sensitivity and delayed epithelialization leading to dry eye syndrome, punctate corneal epitheliopathy, recurrent erosions, persistent epithelial defects, and neurotrophic keratopathy [ 49 , 56 ]. On a histological level, reduction in basal epithelial cell density and size, and increased intercellular space as well as increased corneal epithelial basement membrane thickness and irregularity were demonstrated in diabetic corneas [ 57 , 58 , 59 , 60 , 61 ].…”

“…It is postulated that diabetic ocular changes might be in part explained by the dysregulation of a pathway involving the opioid growth factor (OGF), i.e., [Met5]- enkephalin binding to nuclear-associated receptor (OGFr) [ 62 ]. In diabetes, serum OGF levels are elevated, and insulin may affect the OGF-OGFr axis [ 56 , 63 , 64 ].…”