Glaucoma and macular degeneration may be diseases of the eye, but the experience of vision isn’t limited to these two semi-external organs. Investigational therapeutic approaches have turned their attention to the central nervous system (CNS). Approaches such as these aim to regenerate or bypass the damaged anatomical components of the eye and optic nerve, but experts point out that in order to be successful, these therapies will require a visual network, which resides in the higher brain areas.
Last month, Review of Optometry reported on the results of a single case study published in Nature Medicine in May on optogenetic therapy, a new type of gene therapy for degenerative eye disorders that rewires the ganglion cells in the eye. In the case study, a 58-year-old blind man with retinitis pigmentosa was given limited vision with the therapy and the help of light-stimulating goggles. Therapies such as this rely on intact brain circuitry to ensure correct signal processing.
The increase in research into therapeutic avenues that aim for the restitutio ad integrum—a restoration to original condition—of damaged retinal structures has drawn the attention of researchers in Italy. The team analyzed currently available data in the literature on CNS modifications to identify implications for existing and developing rehabilitation and therapeutic strategies. “There’s much evidence to suggest that the alterations resulting from glaucoma and macular degeneration aren’t limited to the retina alone, but also affect the central nervous system in both structural and functional terms,” they wrote in their paper, published on June 24 in Eye & Brain.
As it turns out, morphological and functional alterations to the CNS do in fact occur in both glaucoma and macular degeneration. The review authors pointed out that in glaucoma, these are limited to the visual areas in macular degeneration while involving multiple brain areas. The causes and mechanisms at the base of these modifications aren’t yet clear.
“The main hypotheses are ascribable to a mechanism of trans-synaptic degeneration linked to functional deprivation following retinal damage; to the activation of normally silent collateral circuits; to involutionary mechanisms similar to those proper to primitive neurodegenerative pathologies such as Alzheimer’s disease and to remodeling through neuronal plasticity,” the researchers noted. “With regard to the last two points, evidence is not yet definitive.”
While the presence of these modifications and the potential for compensatory rehabilitative pathways is somewhat hopeful, the literature suggests it’s also possible that the modifications could hinder some of the therapeutic strategies aimed at restoring the neuroretina currently under development.
“If these modifications weren’t reversible, the change in the neural networks at the basis of the connection existing between the retina and the brain and between the different areas of the brain would hinder the correct processing of the visual signal,” they wrote. “This problem could occur mainly in glaucoma, which shows a widespread involvement in a large part of the CNS, rather than in macular degeneration where the modifications are more isolated at the posterior pole.”
The authors say that further research and evidence is needed to study the alterations in patients. “The results found in current literature weren’t always of unequivocal interpretation, due to the heterogeneity of patients’ characteristics, stage of illness, used stimuli, type of analysis carried out and studied brain areas,” they wrote. “We need to investigate where these changes could be reversible."
Nuzzi R, Vitale A. Cerebral modifications in glaucoma and macular degeneration: analysis of current evidence in literature and their implications on therapeutic perspectives. Eye Brain. 2021;13:159-73.