Identification of Diagnostic and Prognostic microRNAs for Recurrent Vitreous Hemorrhage in Patients with Proliferative Diabetic Retinopathy

Abstract

MicroRNAs (miRNAs) can provide insight into the pathophysiological states of ocular tissues such as proliferative diabetic retinopathy (PDR). In this study, differences in miRNA expression in vitreous from PDR patients with and without incidence of recurrent vitreous hemorrhage (RVH) after the initial pars-plana vitrectomy (PPV) were analyzed, with the aim of identifying biomarkers for RVH. Fifty-four consented vitreous samples were analyzed from patients undergoing PPV for PDR, of which eighteen samples underwent a second surgery due to RVH. Ten of the sixty-six expressed miRNAs (miRNAs-19a, -20a, -22, -27a, -29a, -93, -126, -128, -130a, and -150) displayed divergences between the PDR vitreous groups and to the control. A significant increase in the miRNA-19a and -27a expression was determined in PDR patients undergoing PPV as compared to the controls. miRNA-20a and -93 were significantly upregulated in primary PPV vitreous samples of patients afflicted with RVH. Moreover, this observed upregulation was not significant between the non-RVH and control group, thus emphasizing the association with RVH incidence. miRNA-19a and -27a were detected as putative vitreous biomarkers for PDR, and elevated levels of miRNA-20a and -93 in vitreous with RVH suggest their biomarker potential for major PDR complications such as recurrent hemorrhage incidence.

MicroRNA Expression in the Aqueous Humor of Patients with Diabetic Macular Edema

“…The peculiarity of the present study starts from the population examined: as a matter of fact, AH miRNAs were evaluated in T2D patients affected by DME. Previous studies evaluating miRNA expression through intraocular sampling are few in number and all but one were conducted on patients affected by PDR, in the context of either type 1 or type 2 diabetes [ 16 , 17 , 18 , 19 , 20 ]. We enrolled only patients showing DME with mild or moderate NPDR in an attempt to minimize the ischemic component and consequently the molecular pathways driven by ischemia.…”

“…Hirota et al [ 18 ] investigated the expression of 168 miRNAs in the vitreous humor of patients with PDR and found that six miRNAs (miR-15a, miR-320a, miR-320b, miR-93, miR-29a and miR-423-5p), related to angiogenesis and fibrosis, are significantly overexpressed in PDR. Mammadzada et al [ 19 ] showed a significant increase in the miRNA-19a, miR-27a, miR-20a and miR-93 expression in PDR patients undergoing PPV as compared to the controls. Recently by next generation sequencing, Chen et al [ 20 ] found seven miRNAs upregulated (miR-150-5p, miR-30c-5p, miR16-2-3p, miR-1827, miR-140-3p and miR-93-5p) and one downregulated (miR-99-5p) in AH of T2D patients with PDR as compared to controls.…”

“…The four previous studies evaluating miRNA expression in the vitreous of PDR patients relied on patients affected by macular hole as the control group [ 16 , 17 , 18 , 19 ]. Chen et al [ 20 ], in the evaluation of miRNAs expression of PDR patients, and Cho et al [ 22 ], in the evaluation of miRNA expression in the AH of DME patients, used cataract patients as the control group.…”

“…Investigations using human intraocular samples (vitreous and aqueous humor) are even rarer. Gomaa et al [ 16 ] sampled the vitreous, evaluating miR-200b expression in both T1D and T2D patients, while Usui-Ouchi et al [ 17 ], Hirota et al [ 18 ] and Mammadzada et al [ 19 ] evaluated the expression of multiple miRNAs through a microarray or PCR array vitreal profile. Recently, Chen et al [ 20 ] performed next generation sequencing to evaluate multiple miRNA expression in AH of T2D patients.…”

MicroRNAs: Potential Targets in Diabetic Retinopathy

“…In ▶ table 1, we have summarized miR-126 [11,12], miR-211 [13], miR-93 [14][15][16], miR-122 [17], miR-221 [18], miR-27b and miR-320a [8], miR-150-5p, miR-21-3p and miR-30b-5p [19] as biomarkers in DR over the past 5 years. At the same time, we have focused on miRNAs in vitreous humor (VH) of DR, such as miR-126 [20], miR-19a and 27a [21], miR-29a [22,23], miR-93 and 20a [21], and miR-200b [24] in ▶ table 2.…”