Abstract
Purpose :
Ghrelin is an acidic acylated peptide produced in several organs that binds the growth hormone secretagogue receptor-1a (GHSR-1a). It exerts a plethora of physiological effects, especially on endocrine, cardiovascular and immune systems. At the ocular level, ghrelin is produced locally in the retina, whereas GHSR-1a is abundantly expressed in retinal endothelial cells. It is implicated in the control of the iris, promoting the relaxation of the iris sphincter and dilator muscles. Moreover it can reduce intraocular pressure in animal models of ocular hypertension and it has antioxidant and neuroprotective effects on the retina inhibiting retinal autophagy, ganglion cell apoptosis, and Müller cell gliosis. It has been shown also that it can exert opposing effects on retinal vasculature, depending on the type and phase of retinopathy. However, to date, the role of ghrelin in human diabetes-induced retinal damage has not been investigated yet.
Methods :
We studied the serum levels of total ghrelin (TG), its acylated (AG) and des-acylated (DAG) forms in patients affected by different stages of diabetic retinopathy (DR). We also investigated the correlation between serum TG and neutrophil elastase (NE), a serine protease released by activated neutrophils and potentially implicated in the capillary degeneration in the initial stages of DRs, with consequent increased risk of retinal microhemorrhages. Using Enzyme-Linked ImmunoSorbent Assays (ELISA) we analyzed the serum levels of ghrelin and NE respectively in: a) 12 non-diabetic subjects (CTRL); b) 15 diabetic patients without signs of DR (Diabetic); 15 patients with non-proliferative DR (NPDR) and 15 patients with proliferative DR (PDR).
Results :
Serum TG and AG levels were significantly decreased in NPDR patients (P<0.01 vs Diabetic) and PDR patients (P<0.01 vs NPDR). Serum AG levels were inversely associated with DR progression (r = -0.83, P<0.01), serum neutrophils percentage (r = -0.74, P<0.01), and serum NE levels (r = -0.73, P<0.01). Furthermore, NE serum levels were significantly increased in the NPDR (P < 0.01 vs diabetic) and PDR (P<0.01 vs PDR) groups, positively correlating with DR progression (r=0.86, P < 0.01).
Conclusions :
Reduced serum levels of circulating AG with concomitant high serum levels of NE are correlated with an increased risk of retinal microhemorrhages and DR worsening, and therefore could be considered a new systemic biomarker of DR progression.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.