MITOCHONDRIAL QUALITY CONTROL IN NON EXUDATIVE AGE RELATED MACULAR DEGENERATION: FROM MOLECULAR MECHANISMS TO STRUCTURAL AND FUNCTIONAL RECOVERY

DIEGUEZ HH.; ALAIMO, A.; CALANNI, JS.; BERNAL AGUIRRE, NA.; CHIANELLI, MS.; SCIURANO, R.; ROSENSTEIN RE, DORFMAN D; ROMEO, HE

Mar del Plata

Congreso; LXVIII Reunion Anual de Sociedad Argentina de Investigacion Clinica (SAIC); 2023

Sociedad Argentina de Investigacion Clinica (SAIC)

Nonexudat ive age related macular degeneration (NE AMD) is the leadingblindness cause in the elderly. Clinical and experimental evidence supports thatearly alterations in macular retinal pigment epithelium (RPE) mitochondria playa key role in NE AMD induced damag e. Mitochondrial dynamics (biogenesis,fusion, fission, and mitophagy) determines mitochondrial quality, which is, inturn, under a central control of AMP activated kinase (AMPK). We havedeveloped a NE AMD model in C57BL/6J mice induced by unilateral supe riorcervical ganglionectomy (SCGx), which reproduces the disease hallmarks onlyat the macula like (temporal) region of the RPE/outer retina. Our aim wasstudying RPE mitochondria structure, dynamics, function, and AMPKinvolvement on these parameters at an early stage of experimental NE AMD .Histological, ultrastructural, and biochemical parameters of the nasal andtemporal RPE were studied at 4 and 10 weeks post SCGx. RPE mitochondriamass was preserved, but their function (by TMRE fluorescence) at the temporalRPE, which was higher than at the nasal RPE in sham eyes, was significantlydecreased at 4 weeks post SCGx (**P<0.01 vs. sham, by Tukey). At structurallevel, mitochondria were bigger, more elongated and with denser cristae at thetemporal RPE fr om sham eyes. SCGx drastically affected mitochondrialmorphology, together with the levels of phosphorylated AMPK (pAMPK), only atthe temporal RPE (**P<0.01 vs. sham, by Tukey). Moreover, SCGx induced adecrease in mitochondria dynamics at the temporal R PE (**P<0.01 vs. sham,by Tukey). A group of animals was treated with 100 mg/kg metformin (an AMPKactivator) for 10 weeks. Metformin restored the levels of pAMPK, as well asmitochondrial dynamics, structure, and functionality at 4 weeks post SCGx, andv isual function and RPE/outer retina structure at 10 weeks post SCGx. Theseresults demonstrate AMPK activation role in RPE mitochondria homeostasisand the protective effect of metformin in NE AMD.