310 - Comparison of gene up regulation between a mouse model of ROP and extremely premature newborns from days 7 to 14 of life.

Publication Number: 4304.310

Nitin Chouthai, Oakland University William Beaumont School of Medicine, Dearborn, MI, United States; Nikhlesh K. Singh, Wayne State University School of Medicine, Detroit, MI, United States

Background: Severe ROP is linked to considerable morbidity in extremely premature newborns. To our knowledge, there are currently no early-phase biomarkers for ROP.

Objective: The objective of this retrospective study was to compare the retinal RNA expression in mouse pups exposed to oxygen-induced retinopathy with the blood RNA profile of extremely premature newborns during the first two weeks of life, specifically from days 7 to 14 of life.

Design/Methods: Bulk RNA transcriptome analysis was conducted using peripheral blood samples from 21 extremely preterm newborns who were born at less than 26 weeks’ gestation and were between 7 and 14 days of life. Additionally, an early-phase transcriptome was performed on the retina of a murine model of oxygen- induced retinopathy. RNA expression profiles from both the data sets were analyzed for comparison. Newborns born at < 26 weeks without ROP and mouse pups that are exposed to room air of same age serves as controls for preterm infants and for oxygen-induced retinopathy, respectively.

Results: We observed a significant upregulation of fibroblast growth factor 2 (FGF2), PLOD2 (procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2), transgalin-2 (Tagln 2), nuclear protein 1, transcriptional regulator (Nupur1), and PFKB3 (6-phosphofructo-2- kinase and fructose-2,6-bisphosphatase) in the blood of severe/mild ROP patients, as well as in the retinas of mouse models of oxygen-induced retinopathy, compared to their respective controls. FGF2 plays multiple roles in biological processes, including cell proliferation, development, wound healing, and angiogenesis. PLOD2 is a crucial enzyme that mediates the formation of stabilized collagen crosslinks, and its high expression is linked to immune cell infiltration and cancer progression. Tagln 2, and Nupur1 are proposed to play a role in tumor angiogenesis. PFKB3 is a key regulator of glycolysis, and its elevated expression indicates a of disturbance in endothelial cell metabolic pathways, which can lead to pathological angiogenesis.

Conclusion(s): PLOD2 may be a potential target for retinopathy of prematurity (ROP), a condition marked by increased migration of inflammatory cells to the retina and heightened inflammation in the retinas of ROP patients. Tagin 2 and Nupur1 could serve as potential targets for inhibiting angiogenesis in ROP patients, given that inflammation is a significant contributor of ROP related retinal neovascularization. PFKFB3 might represent a viable target for angiogenic therapies aimed at preserving endothelial cell function and preventing ROP pathophysiology.