Sequences of Alterations in Inflammation and Autophagy Processes in Rd1 Mice
Javier Martínez-González,
Ángel Fernández-Carbonell,
Antolin Cantó,
Roberto Gimeno-Hernández,
Inmaculada Almansa,
Francisco Bosch-Morell,
María Miranda,
Teresa Olivar
Affiliations
Javier Martínez-González
Department of Biomedical Sciences, Faculty of Health Sciences, Institute of Biomedical Sciences, Cardenal Herrera-CEU University, CEU Universities, 46115 Valencia, Spain
Ángel Fernández-Carbonell
Department of Biomedical Sciences, Faculty of Health Sciences, Institute of Biomedical Sciences, Cardenal Herrera-CEU University, CEU Universities, 46115 Valencia, Spain
Antolin Cantó
Department of Biomedical Sciences, Faculty of Health Sciences, Institute of Biomedical Sciences, Cardenal Herrera-CEU University, CEU Universities, 46115 Valencia, Spain
Roberto Gimeno-Hernández
Department of Biomedical Sciences, Faculty of Health Sciences, Institute of Biomedical Sciences, Cardenal Herrera-CEU University, CEU Universities, 46115 Valencia, Spain
Inmaculada Almansa
Department of Biomedical Sciences, Faculty of Health Sciences, Institute of Biomedical Sciences, Cardenal Herrera-CEU University, CEU Universities, 46115 Valencia, Spain
Francisco Bosch-Morell
Department of Biomedical Sciences, Faculty of Health Sciences, Institute of Biomedical Sciences, Cardenal Herrera-CEU University, CEU Universities, 46115 Valencia, Spain
María Miranda
Department of Biomedical Sciences, Faculty of Health Sciences, Institute of Biomedical Sciences, Cardenal Herrera-CEU University, CEU Universities, 46115 Valencia, Spain
Teresa Olivar
Department of Biomedical Sciences, Faculty of Health Sciences, Institute of Biomedical Sciences, Cardenal Herrera-CEU University, CEU Universities, 46115 Valencia, Spain
(1) Background: the aim of this work was to study microglia and autophagy alterations in a one retinitis pigmentosa (RP) model at different stages of the disease (when rods are dying and later, when there are almost no rods, and cones are the cells that die. (2) Methods: rd1 mice were used and retinas obtained at postnatal days (PN) 11, 17, 28, 35, and 42. Iba1 (ionized calcium-binding adapter molecule 1) was the protein selected to study microglial changes. The macroautophagy markers Beclin-1, Atg5, Atg7, microtubule-associated protein light chain 3 (LC3), and lysosomal-associated membrane protein 2 (LAMP2) (involved in chaperone-mediated autophagy (CMA)) were determined. (3) Results: the expression of Iba1 was increased in rd1 retinas compared to the control group at PN17 (after the period of maximum rod death), PN28 (at the beginning of the period of cone death), and PN42. The number of activated (ameboid) microglial cells increased in the early ages of the retinal degeneration and the deactivated forms (branched cells) in more advanced ages. The macroautophagy markers Atg5 at PN11, Atg7 and LC3II at PN17, and Atg7 again at PN28 were decreased in rd1 retinas. At PN35 and PN42, the results reveal alterations in LAMP2A, a marker of CMA in the retina of rd1 mice. (4) Conclusions: we can conclude that during the early phases of retinal degeneration in the rd1 mouse, there is an alteration in microglia and a decrease in the macroautophagy cycle. Subsequently, the CMA is decreased and later on appears activated as a compensatory mechanism.
