Fotoreceptorapoptose

Fotoreceptorapoptose, or photoreceptor apoptosis, refers to the programmed death of retinal photoreceptors—rods and cones—in response to cellular stress. It is a central mechanism in many retinal diseases and contributes to progressive vision loss.

Mechanistically, fotoreceptorapoptose can proceed through intrinsic mitochondrial pathways and, in some contexts, through extrinsic death receptor pathways. Stress such as oxidative damage, calcium dysregulation, metabolic insufficiency, or misfolded proteins can trigger mitochondrial outer membrane permeabilization, cytochrome c release, formation of the apoptosome, and activation of executioner caspases (for example, caspase-9 and caspase-3). The extrinsic pathway involves activation of caspase-8 via tumor necrosis factor family receptors. Crosstalk between these pathways modulates the final cell fate.

Clinical contexts include inherited retinal degenerations such as retinitis pigmentosa, Leber congenital amaurosis, and cone-rod dystrophy; age-related macular degeneration; diabetic retinopathy; retinal detachment; and light-induced retinal injury. In these conditions, photoreceptor loss reduces outer nuclear layer thickness and impairs the retinal circuitry, leading to progressive vision decline.

Detection of photoreceptor apoptosis in research and, to some extent, clinical settings uses histological methods such as TUNEL labeling, along with markers of caspase activation. Functionally, electroretinography shows reduced rod and/or cone responses corresponding to loss of photoreceptors.

Therapeutic approaches aim to slow or block fotoreceptorapoptose and thereby preserve vision. These include gene therapy to correct disease-causing mutations, neuroprotective strategies, antioxidants to limit oxidative stress, and experimental caspase inhibitors or anti-apoptotic agents studied in animal models. Understanding the timing and regulation of photoreceptor apoptosis remains a priority for developing durable retinal therapies.