Neuronal and glial cell changes are determined by retinal vascularization in retinopathy of prematurity.

We have characterized the vascular, neuronal, and glial changes in oxygen-induced retinopathy, a model of retinopathy of prematurity (ROP). Newborn Sprague-Dawley rats were exposed to either 80% +/- 2% oxygen to postnatal day P11 and then room air until P18 (ROP) or room air for the entire duration (controls). Retinal structure was examined under the light microscope and following postembedding immunocytochemistry in central, midperipheral, and peripheral regions. Müller cells were evaluated immunocytochemically with glial fibrillary acidic protein. The extent of vascularization was established histologically. ROP caused significant thinning of the inner cellular and plexiform layers, which became more pronounced in the peripheral inner nuclear layer of ROP animals (11.3% loss vs. 25.4% loss). Amacrine cell amino acid levels were particularly vulnerable in the peripheral retina; bipolar cells showed similar but less prominent changes. Müller cells had elevated glutamine levels and were most gliotic in the periphery. The vasculature extended to peripheral retinal regions at P18 in controls but not in ROP rats. The most striking pattern of change was evident in the midperipheral "transition zone" of ROP animals. Areas close to blood vessels showed neurochemical properties that were similar to those of the central retina, indicating a local protective effect of the inner retinal blood supply. We find that ROP produces complex vascular, neural, and glial changes that relate to the proximity of inner retinal blood vessels.

Downie LE ，Pianta MJ ，Vingrys AJ ，Wilkinson-Berka JL ，Fletcher EL ... -  《JOURNAL OF COMPARATIVE NEUROLOGY》

Effects of sustained hyperoxia on revascularization in experimental retinopathy of prematurity.

Gu X ，Samuel S ，El-Shabrawey M ，Caldwell RB ，Bartoli M ，Marcus DM ，Brooks SE ... -  《INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE》

Angiotensin type-1 receptor inhibition is neuroprotective to amacrine cells in a rat model of retinopathy of prematurity.

Downie LE ，Hatzopoulos KM ，Pianta MJ ，Vingrys AJ ，Wilkinson-Berka JL ，Kalloniatis M ，Fletcher EL ... -  《-》

Localization of adenosine A2a receptor in retinal development and oxygen-induced retinopathy.

Taomoto M ，McLeod DS ，Merges C ，Lutty GA ... -  《INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE》

Characterization of retinal function and glial cell response in a mouse model of oxygen-induced retinopathy.

Retinal neovascularization, such as that occurring in proliferative diabetic retinopathy and retinopathy of prematurity, can have serious effects on visual function. By using a mouse model of neovascularization, oxygen-induced retinopathy (OIR), the interplay among angiogenesis, neuronal function, and the macro- and micro-glial response was explored. OIR was induced by exposure of mice to 75% oxygen from postnatal day 7 (P7) to P11 and then room air until P18. Controls were reared in room air. Blood vessel development was assessed by using fluorescence histochemistry. Aberrant intravitreal neovascularization was present across all eccentricities of retina in mice with OIR, whereas the number of vessels present in the deep plexus was reduced in the central regions. Neuronal function of both the rod and cone pathways, assessed by using the electroretinogram, was found to be significantly reduced in OIR. This may in part be explained by an alteration in photoreceptor outer segment morphology and also a loss of neurons and their synapses in the inner nuclear and plexiform layers of the central retina. In addition, there was an increase in the number of gliotic Müller cells and microglia in mice with OIR and the increase in the number of these cells correlated with the absence of the deep plexus. This indicates that the activity of both macro- and microglia is altered in regions where the deep plexus blood supply is deficient. Treatments or genetic manipulations directed toward amelioration of proliferative retinopathy need to address not only the vascular changes but also the alterations in neuronal and macro- and microglial function.

Vessey KA ，Wilkinson-Berka JL ，Fletcher EL 《-》