Neuroprotective Effects of FGF2 and Minocycline in Two Animal Models of Inherited Retinal Degeneration
| Autor: | Marta Agudo-Barriuso, Thomas Langmann, María Paz Villegas-Pérez, Manuel Vidal-Sanz, Diego García-Ayuso, M.C. Sánchez-Migallón, Johnny Di Pierdomenico, F Javier Valiente-Soriano, Rebecca Scholz |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Retinal degeneration Cell Survival Minocycline Pharmacology Ciliary neurotrophic factor Rats Sprague-Dawley 03 medical and health sciences chemistry.chemical_compound PEDF Neurotrophic factors medicine Animals Ciliary Neurotrophic Factor Nerve Growth Factors Outer nuclear layer Eye Proteins Fluorescent Antibody Technique Indirect Serpins Microglia biology Retinal Degeneration Retinal medicine.disease Anti-Bacterial Agents Rats Disease Models Animal 030104 developmental biology medicine.anatomical_structure Neuroprotective Agents chemistry Intravitreal Injections biology.protein Drug Therapy Combination Fibroblast Growth Factor 2 sense organs Injections Intraperitoneal medicine.drug |
| Zdroj: | Investigative ophthalmologyvisual science. 59(11) |
| ISSN: | 1552-5783 |
| Popis: | Purpose The purpose of this study was to study the effect of minocycline and several neurotrophic factors, alone or in combination, on photoreceptor survival and macro/microglial reactivity in two rat models of retinal degeneration. Methods P23H-1 (rhodopsin mutation), Royal College of Surgeon (RCS, pigment epithelium malfunction), and age-matched control rats (Sprague-Dawley and Pievald Viro Glaxo, respectively) were divided into three groups that received at P10 for P23H-1 rats or P33 for RCS rats: (1) one intravitreal injection (IVI) of one of the following neurotrophic factors: ciliary neurotrophic factor (CNTF), pigment epithelium-derived factor (PEDF), or basic fibroblast growth factor (FGF2); (2) daily intraperitoneal administration of minocycline; or (3) a combination of IVI of FGF2 and intraperitoneal minocycline. All animals were processed 12 days after treatment initiation. Retinal microglial cells and cone photoreceptors were immunodetected and analyzed qualitatively in cross sections. The numbers of microglial cells in the different retinal layers and number of nuclei rows in the outer nuclear layer (ONL) were quantified. Results IVI of CNTF, PEDF, or FGF2 improved the morphology of the photoreceptors outer segment, but only FGF2 rescued a significant number of photoreceptors. None of the trophic factors had qualitative or quantitative effects on microglial cells. Minocycline treatment reduced activation and migration of microglia and produced a significant rescue of photoreceptors. Combined treatment with minocycline and FGF2 had higher neuroprotective effects than each of the treatments alone. Conclusions In two animal models of photoreceptor degeneration with different etiologies, minocycline reduces microglial activation and migration, and FGF2 and minocycline increase photoreceptor survival. The combination of FGF2 and minocycline show greater neuroprotective effects than their isolated effects. |
| Databáze: | OpenAIRE |
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