PURPOSE: Dilated and tortuous vessels (plus disease) in ROP is a grim prognostic indicator of visual outcome. The purpose of this study was to determine whether alterations in pericytes and smooth muscle cells (SMCs), are associated with the pathogenesis of ROP, including plus disease. METHODS: Kittens were exposed to either 4 (standard obliterative model) or 2 (modified model) days of hyperoxia, resulting in vaso-obliteration or localized vessel regression, respectively, and returned to room air. The modified model more closely resembles human ROP. Desmin and alpha-smooth muscle actin (SMA) immunohistochemistry and lectin labeling were used to label mural cells and vessels. The desmin ensheathment ratio (DER), a quantitative measure of vessel stability, was determined. RESULTS: In the neovasculature of the standard model and surviving vasculature of the modified model, radial arterioles and venules were dilated and SMCs attenuated. SMA expression on venules was decreased, and the difference in desmin expression normally observed between arterioles and venules was lost, indicating altered SMC differentiation. The DER was reduced in both ROP models, consistent with highly unstable vascular plexuses, receptive to angiogenic and vascular regression signals. CONCLUSIONS: The results provide compelling evidence of significant changes in arteriolar and venular SMCs in both experimental models of ROP. The delayed differentiation and apparent dedifferentiation of SMCs during the hypoxic phases would result in an impaired ability to regulate blood flow, contributing to the vasodilation and tortuosity, hallmarks of plus disease. Vessel tortuosity was seen only in the nonobliterative model, suggesting that tortuosity may be due to increased capillary resistance resulting from capillary closure.
PURPOSE: Dilated and tortuous vessels (plus disease) in ROP is a grim prognostic indicator of visual outcome. The purpose of this study was to determine whether alterations in pericytes and smooth muscle cells (SMCs), are associated with the pathogenesis of ROP, including plus disease. METHODS: Kittens were exposed to either 4 (standard obliterative model) or 2 (modified model) days of hyperoxia, resulting in vaso-obliteration or localized vessel regression, respectively, and returned to room air. The modified model more closely resembles human ROP. Desmin and alpha-smooth muscle actin (SMA) immunohistochemistry and lectin labeling were used to label mural cells and vessels. The desmin ensheathment ratio (DER), a quantitative measure of vessel stability, was determined. RESULTS: In the neovasculature of the standard model and surviving vasculature of the modified model, radial arterioles and venules were dilated and SMCs attenuated. SMA expression on venules was decreased, and the difference in desmin expression normally observed between arterioles and venules was lost, indicating altered SMC differentiation. The DER was reduced in both ROP models, consistent with highly unstable vascular plexuses, receptive to angiogenic and vascular regression signals. CONCLUSIONS: The results provide compelling evidence of significant changes in arteriolar and venular SMCs in both experimental models of ROP. The delayed differentiation and apparent dedifferentiation of SMCs during the hypoxic phases would result in an impaired ability to regulate blood flow, contributing to the vasodilation and tortuosity, hallmarks of plus disease. Vessel tortuosity was seen only in the nonobliterative model, suggesting that tortuosity may be due to increased capillary resistance resulting from capillary closure.
Authors: Victor H Guaiquil; Nina J Hewing; Michael F Chiang; Mark I Rosenblatt; R V Paul Chan; Carl P Blobel Journal: Invest Ophthalmol Vis Sci Date: 2013-08-07 Impact factor: 4.799
Authors: Thomas A Mendel; Erin B D Clabough; David S Kao; Tatiana N Demidova-Rice; Jennifer T Durham; Brendan C Zotter; Scott A Seaman; Stephen M Cronk; Elizabeth P Rakoczy; Adam J Katz; Ira M Herman; Shayn M Peirce; Paul A Yates Journal: PLoS One Date: 2013-05-31 Impact factor: 3.240
Authors: Ronald H Silverman; Raksha Urs; Danny H-Kauffmann Jokl; Leora Pinto; Osode Coki; Rakesh Sahni; Jason D Horowitz; Steven E Brooks Journal: Transl Vis Sci Technol Date: 2021-02-05 Impact factor: 3.048