Functional and morphological alterations in a glaucoma model of acute ocular hypertension

To study short and long-term effects of acute ocular hypertension (AOHT) on inner and outer retinal layers, in adult Sprague-Dawley rats AOHT (87mmHg) was induced for 90min and the retinas were examined longitudinally in vivo with electroretinogram (ERG) recordings and optical coherent tomography (OCT) from 1 to 90 days (d). Ex vivo, the retinas were analyzed for rod (RBC) and cone (CBC) bipolar cells, with antibodies against protein kinase Cα and recoverin, respectively in cross sections, and for cones, horizontal (HZ) and ganglion (RGC) cells with antibodies against arrestin, calbindin and Brn3a, respectively in wholemounts. The inner retina thinned progressively up to 7d with no further changes, while the external retina had a normal thickness until 30d, with a 20% thinning between 30 and 90d. Functionally, the a-wave showed an initial reduction by 24h and a further reduction from 30 to 90d. All other main ERG waves were significantly reduced by 1d without significant recovery by 90d. Radial sections showed a normal population of RBCs but their terminals were reduced. The CBCs showed a progressive decrease with a loss of 56% by 30d. In wholemount retinas, RGCs diminished to 40% by 3d and to 16% by 30d without further loss. Cones diminished to 58% and 35% by 3 and 7d, respectively and further decreased between 30 and 90d. HZs showed normal values throughout the study. In conclusion, AOHT affects both the inner and outer retina, with a more pronounced degeneration of the cone than the rod pathway.