Pharmacological strategies in retinal dystrophies

Abstract

AbstractThe therapeutic options for a patient affected by a retinal degenerative disease are discouraging. Despite several clinical trials show promising results, we still need to go a long way until the arrival to the clinics of therapies that could partially restore the retinal functionality, as optogenetics, or stem cell transplant, or, even better, that cure the disease by targeting its aetiology, as gene therapy. Until these therapies reach clinical success, targeting key factors in the degenerative process could temporarily slow its progression. Although there are many different retinal degenerative diseases, with different aetiology and clinical evolution, the degenerative process is always accompanied by common biochemical and molecular factors, it does not matter if the degeneration has a genetic cause, as it happens in inherited retinal dystrophies as retinitis pigmentosa, Leber congenital amaurosis or Stargardt disease; or if it is a multifactorial disease as age‐related macular degeneration; or if it is secondary to other pathologies, as diabetic retinopathy. The high metabolic rate of the retinal cells, their continuous exposition to high oxygen levels and light‐induced stress are key factors in the development of the degenerative process. When retinal cells start to die, activated glial cells secrete proinflammatory cytokines, chemokines and trophic factors that worsen the degenerative process. Thus, trying to reduce the oxidative stress and inflammation that are always present in the degenerating tissue seems a good approach to be tried. Moreover, considering the great number of mediators involved in the degenerative process, a widest approach combining therapies with antioxidant, anti‐inflammatory and antiapoptotic molecules, as well as neurotrophic factors could slow the progression of the disease and preserve the visual capacity for a certain time. Moreover, even when the vision has been completely lost, the neuroprotection could improve other non‐visual functions, like the control of circadian rhythms and pupil contraction and could also influence the patient's memory and mood. It is also relevant to note that this therapy can keep a healthy tissue and provide an adequate environment of healthy cells that will help to the clinical success of other techniques as cell transplant or optogenetic approaches, which could hardly be successful in a damaged tissue surrounded by dying cells.Supported by: Spanish Ministry of Science and Innovation (MICINN‐FEDER PID2019‐106230RB‐I00) Generalitat Valenciana (PROMETEO/2021/024).