Universität zu Köln

Di Pierdomenico, Johnny, Scholz, Rebecca, Javier Valiente-Soriano, F., Sanchez-Migallon, Maria C., Vidal-Sanz, Manuel, Langmann, Thomas, Agudo-Barriuso, Marta ORCID: 0000-0002-8566-9277, Garcia-Ayuso, Diego ORCID: 0000-0002-7639-5366 and Paz Villegas-Perez, Maria (2018). Neuroprotective Effects of FGF2 and Minocycline in Two Animal Models of Inherited Retinal Degeneration. Invest. Ophthalmol. Vis. Sci., 59 (11). S. 4392 - 4404. ROCKVILLE: ASSOC RESEARCH VISION OPHTHALMOLOGY INC. ISSN 1552-5783

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Abstract

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: clliary 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 (ONE) were quantified. RESULTS. IVI of CNTF, PEDF, or FGF2 Unproved 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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Di Pierdomenico, Johnny UNSPECIFIED UNSPECIFIED UNSPECIFIED Scholz, Rebecca UNSPECIFIED UNSPECIFIED UNSPECIFIED Javier Valiente-Soriano, F. UNSPECIFIED UNSPECIFIED UNSPECIFIED Sanchez-Migallon, Maria C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Vidal-Sanz, Manuel UNSPECIFIED UNSPECIFIED UNSPECIFIED Langmann, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Agudo-Barriuso, Marta UNSPECIFIED orcid.org/0000-0002-8566-9277 UNSPECIFIED Garcia-Ayuso, Diego UNSPECIFIED orcid.org/0000-0002-7639-5366 UNSPECIFIED Paz Villegas-Perez, Maria UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-175028
DOI:	10.1167/iovs.18-24621
Journal or Publication Title:	Invest. Ophthalmol. Vis. Sci.
Volume:	59
Number:	11
Page Range:	S. 4392 - 4404
Date:	2018
Publisher:	ASSOC RESEARCH VISION OPHTHALMOLOGY INC
Place of Publication:	ROCKVILLE
ISSN:	1552-5783
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language FIBROBLAST-GROWTH-FACTOR; HUMAN RETINITIS-PIGMENTOSA; EPITHELIUM-DERIVED FACTOR; MICROGLIAL CELLS; MOUSE MODEL; PHOTORECEPTOR CELLS; ACTIVATED MICROGLIA; RIBOZYME RESCUE; TRANSGENIC RAT; ROYAL-COLLEGE Multiple languages Ophthalmology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/17502