Structural And Functional Changes Of Primary Visual Cortex In Mice With Glaucoma

Glaucoma is a highly blinding eye degenerative disease that causes damage to retinal ganglion cells(RGCs),optic nerve head and retinal nerve fiber layer(RNFL),resulting in irreversible vision loss.There are evidences that eye degeneration is related to brain degeneration,which could be examined by the biomarkers in cerebral cortex,and cortical neural activity,biomarkers such as amyloid β-protein(Aβ)and hyperphosphorylated Tau protein(p-Tau).Althought previous studies have reported that glaucoma may lead to brain degeneration,the degeneration in the primary visual cortex(V1)is not well investigated in the DBA/2J model,which is an important genetic models of glaucoma disease.Therefore,exploring the V1 degeneration caused by DBA/2J model of glaucoma can provide more insight to better understand the link between eye degeneration and brain degeneration.In this study,10-month-old DBA/2J mice were used to evaluate retinal degeneration,and biomarkers associated with degeneration within V1 and neural activity in V1 were studied.In the evaluation of retinal degeneration,RGCs,RNFL,Aβ,p-Tau,and microglia in the retina were compared using tissue sections and staining techniques.In the V1,Aβ,p-Tau,microglia,nissl body,and neuron nucleus(Neu N)were quantified and compared.Besides,the spontaneous activity and tuning curves respond to visual features(orientation,spatial frequency,temporal frequency,contrast function)were investigated for V1 neurons by in vivo two-photon imaging.Compared with the control group,DBA/2J mice had a little number of RGCs,thin RNFL thickness,a large number of p-Tau positive cells and microglia in the retina,showing similar damage to glaucoma patients.DBA/2J mice had a little number of nissl body and Neu N positive neurons in V1 neurons,which indicate that the number of neurons is few.The number of p-Tau positive neurons and microglia in DBA/2J mice V1 was large,and Aβ has a tendency to increase,which was manifested as damage similar to neurodegenerative diseases.Compared with the control group,the neuronal calcium signals collected by DBA/2J mice V1 were more active,with weak orientation selectivity,low optimal spatial frequency and high optimal time frequency,indicating that the visual function of DBA/2J mice was affected.Our result have shown the DBA/2J model of glaucoma have significant degeneration both in retina and V1.These results also provide more evidence for the brain degeneration caused by glaucoma,and also make more useful exploration of the link between eye degeneration and brain degeneration.