Recent research suggests that retinal changes occur at early stages of Alzheimer's disease (AD). However, gaps remain in understanding the detailed pathophysiological processes and their molecular underpinnings.
Objective
This study investigates alterations in the retinal neurovascular unit (NVU) and associated proteomic changes in the TgF344-AD rat model to determine how these changes relate to brain and known AD pathology.
Methods
Transgenic rats and age-matched wild-type rats were studied. Proteomic analysis was conducted to identify changes in critical signaling pathways across the retina, the visual sensory thalamus (the lateral geniculate body, LGN) and hippocampus. Immunofluorescence staining was used to detect amyloid-β, glial, neuronal and vascular markers in the retina, and p-phenylenediamine staining examined axons of retinal ganglion cells.
Results
Significant axonal degeneration in the optic nerve and optic tract of AD rats was detected, while axonal integrity in the optic chiasm, retinal ganglion cell numbers and retinal layer thickness remained unaffected. Proteomics showed a general downregulation of pathways essential for neural survival, glial function and vascular stability, with striking similarities between the retina and LGN. A significant reduction in amacrine cell numbers, increased microglial reactivity, decreased Müller cell immunoreactivity and reduced retinal pericyte density were also observed.
Conclusions
These findings suggest that retrograde and anterograde axonal degeneration, coupled with NVU dysfunction, are key features of retinal pathology in AD. The TgF344-AD rat model provides valuable insights into these changes, highlighting the retina as a potential site for early AD detection, monitoring and intervention.
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