ENRICHED ENVIRONMENT PROTECTS THE CENTRAL OUTER RETINA AGAINST EXPERIMENTAL NON-EXUDATIVE AGE-RELATED MACULAR DEGENERATION IN MICE

DAMIAN DORFMAN, NATHALY BERNAL AGUIRRE, JUAN S. CALANNI, RUTH E. ROSENSTEIN, HERNÁN H. DIEGUEZ; HORACIO E. ROMEO; AGUSTINA ALAIMO

Mar del Plata

Congreso; LXVII REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INVESTIGACIÓN CLÍNICA (SAIC); 2022

SAIC

Non-exudative age-related macular degeneration(NE-AMD), the main cause of blindness in the elderly, ischaracterized by retinal pigment epithelium (RPE) and photoreceptors (PR)atrophy circumscribed to the macular area. There are no effective therapies to preventor delay the vision loss that affects patients with NE-AMD.We have developed a NE-AMD model induced bysuperior cervical ganglionectomy (SCGx) in C57BL/6J mice, which reproduces the disease hallmarks exclusively circumscribed to the temporal regionof the RPE/PR. Environmental enrichment (EE) is a complex combination of physical and inanimate stimulation, which has provenneuroprotective effects against retinal neurodegeneration. The aimof this work was analysing the protective effect of the exposure toEE on the alterations induced by experimental NE-AMD. Adult maleC57BL/6j mice were submitted to unilateral SCGx, whereas thecontralateral side was submitted to a sham procedure. Animals weresubmitted to SCGx and exposed to a standard environment (SE)or EE for 10 weeks. SCGx induced a significant increase in ubiquitouschoroid thickness (p<0.01), a significant decrease in theelectroretinogram a-wave amplitude (p<0.01) and performance invisual behaviour tests (p<0.01), a significant decrease of RPEmelanin content and RPE65-immunoreactivity(p<0.01), a significant decrease in mitochondria mass and increase inmitochondria superoxide and lipid peroxidation products(p<0.01), and RPE and PR ultrastructural alterations at the temporal region.Although, EE did not prevent choroid alterations, it completelypreserved visualfunction, and RPE and PR structure (p<0.01).EE preserved mitochondria mass and structure (p<0.01) and prevented RPEoxidative stress (p<0.01). These results suggest that EE prevented the functionaland structural damage induced by experimental NE-AMD, throughprotecting RPE mitochondria and preventing RPE oxidative damage,thus becoming as a promising therapeutic strategy for NE-AMD@font-face{font-family:Arial;panose-1:2 11 6 4 2 2 2 2 2 4;mso-font-charset:0;mso-generic-font-family:auto;mso-font-pitch:variable;mso-font-signature:3 0 0 0 1 0;}@font-face{font-family:Arial;panose-1:2 11 6 4 2 2 2 2 2 4;mso-font-charset:0;mso-generic-font-family:auto;mso-font-pitch:variable;mso-font-signature:3 0 0 0 1 0;}@font-face{font-family:Calibri;panose-1:2 15 5 2 2 2 4 3 2 4;mso-font-charset:0;mso-generic-font-family:auto;mso-font-pitch:variable;mso-font-signature:3 0 0 0 1 0;}p.MsoNormal, li.MsoNormal, div.MsoNormal{mso-style-unhide:no;mso-style-qformat:yes;mso-style-parent:"";margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;line-height:107%;mso-pagination:widow-orphan;font-size:11.0pt;font-family:Calibri;mso-ascii-font-family:Calibri;mso-ascii-theme-font:minor-latin;mso-fareast-font-family:Calibri;mso-fareast-theme-font:minor-latin;mso-hansi-font-family:Calibri;mso-hansi-theme-font:minor-latin;mso-bidi-font-family:"Times New Roman";mso-bidi-theme-font:minor-bidi;mso-ansi-language:UZ-CYR;}span.markedcontent{mso-style-name:markedcontent;mso-style-unhide:no;}.MsoChpDefault{mso-style-type:export-only;mso-default-props:yes;font-size:11.0pt;mso-ansi-font-size:11.0pt;mso-bidi-font-size:11.0pt;font-family:Calibri;mso-ascii-font-family:Calibri;mso-ascii-theme-font:minor-latin;mso-fareast-font-family:Calibri;mso-fareast-theme-font:minor-latin;mso-hansi-font-family:Calibri;mso-hansi-theme-font:minor-latin;mso-bidi-font-family:"Times New Roman";mso-bidi-theme-font:minor-bidi;mso-ansi-language:UZ-CYR;}.MsoPapDefault{mso-style-type:export-only;margin-bottom:8.0pt;line-height:107%;}div.WordSection1{page:WordSection1;}