Introduction: Elevated intraocular (vitreous) leptin is implicated in proliferative diabetic retinopathy. The source of vitreous leptin is uncertain and it could be derived from systemic leptin. However we showed that leptin (ob) mRNA is present in rat retina, suggesting that retinal tissue could also be a source of intraocular leptin. The present investigation quantified ob mRNA in human retinal tissue obtained from diabetic and control cadavers. In a parallel study, non-diabetic and diabetic patients provided serum and vitreous samples for determination of leptin concentrations.
Methods: Human retinal tissue (CON, n=8; DIAB, n=8) was obtained from the Eye Bank of Canada (Toronto). Ob mRNA was quantified by real-time RT-PCR. Serum and vitreous samples were obtained from diabetic (n=35) and non-diabetic (n=25) patients. Leptin concentrations were determined by radioimmunoassay (Linco Research, Missouri; sensitivity, 0.05 ng/ml).
Results: Serum leptin was not significantly different in DIAB vs CON groups. However differences were seen when male (M) and female (F) groups were compared: F DIAB had higher serum leptin than both CON and M DIAB (P< 0.001), whereas M DIAB vs CON values were not different. In contrast, vitreous levels of leptin were increased in all diabetics (P<0.01) and vitreous leptin levels were also affected by sex; eg. F DIAB values >M DIAB (P<0.001). Ob mRNA was present in all retinal samples. Levels were higher in DIAB vs CON (+60%; P=0.01) and a sex difference was also seen (F>M; P<0.01).
Conclusions: We observed a significant positive effect of diabetes on vitreous leptin levels, especially in females. Since serum leptin was also higher in females compared to males, it suggests that elevated systemic leptin concentrations could be responsible, at least in part, for the high levels observed in vitreous samples from diabetic patients. Nonetheless, we confirmed that human retina might be a source of intraocular leptin, and ob mRNA levels were increased by diabetes in females.
Declaration of funding: This work was supported by UIMRF/Capital Health Research Fund.