Purchase this article with an account.
Sara Rezzola, Mohd Imtiaz Nawaz, Anna Cancarini, Francesco Semeraro, Marco Presta; The vitreous humor from proliferative diabetic retinopathy patients: translational implications. Invest. Ophthalmol. Vis. Sci. 2019;60(9):2661.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Proliferative diabetic retinopathy (PDR), a major complication of diabetes mellitus, represents the main cause of blindness in the Western world. PDR results from the imbalance of pro- and anti-angiogenic factors, being VEGF the most relevant player. Nevertheless, limitations to anti-VEGF therapies do exist and the local production of other growth factors may affect the response to drug treatment. In this frame, PDR vitreous samples may provide information for a better understanding of the pathogenesis of the disease and used for preclinical evaluation of novel drug candidates.
Human vitreous fluid samples were collected fromPDR patients that underwent pars plana vitrectomy. The characterization of their biological activities was assessed in a variety of pro-angiogenic/pro-inflammatory assays. Moreover, drug candidates were evaluated in these assays using PDR vitreous as a pro-angiogenic/pro-inflammatorystimulus.
Our results show that PDR vitreous is able to induce pro-angiogenic/pro-inflammatory responses, including endothelial cell proliferation, migration and vascular remodeling, CREB and NF-kB rapid activation, ROS production, increased permeability and leukocyte adhesion. Also, diabetic vitreous inducesneovessel formation in vivo, being the angiogenic response accompanied by a strong CD45+ inflammatory cell infiltrate. Of note, when PDR vitreous samples were individually probed in an in vitro angiogenesis assay, they exerted a stimulatory response which was characterized by an high heterogeneity related, at least in part, to some preoperative clinical features of the enrolled patients.Finally, molecules with different mechanisms of action (anti-VEGF drugs, biotechnological heparins and bioactive peptides) counteract efficaciously the activity exerted by PDR vitreous on endothelial cells.
The capacity of diabetic vitreous to elicit a potent angiogenic and inflammatory activity represents a useful tool in the study of the pathogenesis of PDR. Congruent with the concept of “metabolic memory”, our data support the hypothesis that PDR vitreous may represent a “reservoir” whose content recapitulates, at least in part, different events that took place during the progression of the disease.Furthermore, the biological activity exerted by PDR vitreous can be used to generate preclinical evidences for the discovery of new pharmacologic approaches.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
This PDF is available to Subscribers Only