CHAPTER 4. CNS Targets for the Treatment of Retinal Dystrophies: A Win–Win Strategy

Abstract

As an extension of the central nervous system (CNS), the retina shares with the brain certain developmental, physiological, and pathological characteristics. However, the underlying mechanisms and pathological signs common to neurodegenerative conditions of both the retina and brain have been relatively overlooked. In animal models and in human patients, marked retinal alterations have been demonstrated in Alzheimer´s disease, Parkinson´s disease, and multiple sclerosis, among other pathologies. Furthermore, neurodegeneration of the retina and brain appears to be mediated by similar mechanisms, which include protein aggregation, neuroinflammation, and cell death. Analysis of the retina, which is easily accessible to objective techniques, may therefore constitute an effective tool for the screening and follow-up of CNS neurodegeneration. Moreover, patients with retinal neurodegeneration could potentially benefit from the broad array of pharmacological compounds that have been designed and tested for the treatment of the aforementioned CNS pathologies. Supporting this view, we have shown that GSK-3 inhibitors, which have already been tested in clinical trials to treat several neurodegenerative conditions of the brain, attenuate retinal damage and vision loss in a mouse model of retinitis pigmentosa. Furthermore, systemic proinsulin treatment preserves visual and cognitive function in mouse models of retinitis pigmentosa and precocious aging, respectively.

The Prohormone Proinsulin as a Neuroprotective Factor: Past History and Future Prospects

“…Based on the observation that neurodegenerative diseases of the brain and retina share several underlying pathological changes, including oxidative stress and neuroinflammation (Cuenca et al, 2014 ; de la Rosa and Hernández-Sánchez, 2019 ), we investigated the effects of injection of AAV vector bearing the human proinsulin gene in the SAMP8 mouse, a model of precocious brain senescence that exhibits several Alzheimer’s disease-like traits (Corpas et al, 2017 ). Proinsulin treatment activated the AKT pathway and decreased expression of neuroinflammation markers in the hippocampus 5 months after injection.…”

Possible Role of Insulin-Degrading Enzyme in the Physiopathology of Retinitis Pigmentosa

“…The retina is a highly specialized part of the central nervous system (CNS) that is responsible for converting light stimuli into chemo-electrical signals, which are then sent to the brain for further processing. As part of the CNS, the retina shares multiple pathophysiological features with the brain [7]. As in the brain, neurodegenerative processes in the retina ultimately cause irreversible loss of neurons, leading to retinal dysfunction and major disabilities.…”