PMID- 25464513 OWN - NLM STAT- MEDLINE DCOM- 20150728 LR - 20231110 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 9 IP - 12 DP - 2014 TI - A novel in vivo model of focal light emitting diode-induced cone-photoreceptor phototoxicity: neuroprotection afforded by brimonidine, BDNF, PEDF or bFGF. PG - e113798 LID - 10.1371/journal.pone.0113798 [doi] LID - e113798 AB - We have investigated the effects of light-emitting diode (LED)-induced phototoxicity (LIP) on cone-photoreceptors and their protection with brimonidine (BMD), brain-derived neurotrophic factor (BDNF), pigment epithelium-derived factor (PEDF), ciliary neurotrophic factor (CNTF) or basic fibroblast growth factor (bFGF). In anesthetized, dark adapted, adult albino rats a blue (400 nm) LED was placed perpendicular to the cornea (10 sec, 200 lux) and the effects were investigated using Spectral Domain Optical Coherence Tomography (SD-OCT) and/or analysing the retina in oriented cross-sections or wholemounts immune-labelled for L- and S-opsin and counterstained with the nuclear stain DAPI. The effects of topical BMD (1%) or, intravitreally injected BDNF (5 microg), PEDF (2 microg), CNTF (0.4 microg) or bFGF (1 microg) after LIP were examined on wholemounts at 7 days. SD-OCT showed damage in a circular region of the superotemporal retina, whose diameter varied from 1,842.4+/-84.5 microm (at 24 hours) to 1,407.7+/-52.8 microm (at 7 days). This region had a progressive thickness diminution from 183.4+/-5 microm (at 12 h) to 114.6+/-6 microm (at 7 d). Oriented cross-sections showed within the light-damaged region of the retina massive loss of rods and cone-photoreceptors. Wholemounts documented a circular region containing lower numbers of L- and S-cones. Within a circular area (1 mm or 1.3 mm radius, respectively) in the left and in its corresponding region of the contralateral-fellow-retina, total L- or S-cones were 7,118+/-842 or 661+/-125 for the LED exposed retinas (n = 7) and 14,040+/-1,860 or 2,255+/-193 for the fellow retinas (n = 7), respectively. BMD, BDNF, PEDF and bFGF but not CNTF showed significant neuroprotective effects on L- or S-cones. We conclude that LIP results in rod and cone-photoreceptor loss, and is a reliable, quantifiable model to study cone-photoreceptor degeneration. Intravitreal BDNF, PEDF or bFGF, or topical BMD afford significant cone neuroprotection in this model. FAU - Ortin-Martinez, Arturo AU - Ortin-Martinez A AD - Departamento de Oftalmologia, Facultad de Medicina, Universidad de Murcia, and Instituto Murciano de Investigacion Biosanitaria Virgen de la Arrixaca (IMIB-Arrixaca), Murcia, Spain. FAU - Valiente-Soriano, Francisco Javier AU - Valiente-Soriano FJ AD - Departamento de Oftalmologia, Facultad de Medicina, Universidad de Murcia, and Instituto Murciano de Investigacion Biosanitaria Virgen de la Arrixaca (IMIB-Arrixaca), Murcia, Spain. FAU - Garcia-Ayuso, Diego AU - Garcia-Ayuso D AD - Departamento de Oftalmologia, Facultad de Medicina, Universidad de Murcia, and Instituto Murciano de Investigacion Biosanitaria Virgen de la Arrixaca (IMIB-Arrixaca), Murcia, Spain. FAU - Alarcon-Martinez, Luis AU - Alarcon-Martinez L AD - Departamento de Oftalmologia, Facultad de Medicina, Universidad de Murcia, and Instituto Murciano de Investigacion Biosanitaria Virgen de la Arrixaca (IMIB-Arrixaca), Murcia, Spain. FAU - Jimenez-Lopez, Manuel AU - Jimenez-Lopez M AD - Departamento de Oftalmologia, Facultad de Medicina, Universidad de Murcia, and Instituto Murciano de Investigacion Biosanitaria Virgen de la Arrixaca (IMIB-Arrixaca), Murcia, Spain. FAU - Bernal-Garro, Jose Manuel AU - Bernal-Garro JM AD - Departamento de Oftalmologia, Facultad de Medicina, Universidad de Murcia, and Instituto Murciano de Investigacion Biosanitaria Virgen de la Arrixaca (IMIB-Arrixaca), Murcia, Spain. FAU - Nieto-Lopez, Leticia AU - Nieto-Lopez L AD - Departamento de Oftalmologia, Facultad de Medicina, Universidad de Murcia, and Instituto Murciano de Investigacion Biosanitaria Virgen de la Arrixaca (IMIB-Arrixaca), Murcia, Spain. FAU - Nadal-Nicolas, Francisco Manuel AU - Nadal-Nicolas FM AD - Departamento de Oftalmologia, Facultad de Medicina, Universidad de Murcia, and Instituto Murciano de Investigacion Biosanitaria Virgen de la Arrixaca (IMIB-Arrixaca), Murcia, Spain. FAU - Villegas-Perez, Maria Paz AU - Villegas-Perez MP AD - Departamento de Oftalmologia, Facultad de Medicina, Universidad de Murcia, and Instituto Murciano de Investigacion Biosanitaria Virgen de la Arrixaca (IMIB-Arrixaca), Murcia, Spain. FAU - Wheeler, Larry A AU - Wheeler LA AD - Zeteo Drug Discovery LLC, Irvine, California, United States of America. FAU - Vidal-Sanz, Manuel AU - Vidal-Sanz M AD - Departamento de Oftalmologia, Facultad de Medicina, Universidad de Murcia, and Instituto Murciano de Investigacion Biosanitaria Virgen de la Arrixaca (IMIB-Arrixaca), Murcia, Spain. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20141202 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Eye Proteins) RN - 0 (Nerve Growth Factors) RN - 0 (Neuroprotective Agents) RN - 0 (Quinoxalines) RN - 0 (Serpins) RN - 0 (pigment epithelium-derived factor) RN - 103107-01-3 (Fibroblast Growth Factor 2) RN - 4S9CL2DY2H (Brimonidine Tartrate) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor/*pharmacology MH - Brimonidine Tartrate MH - Cell Survival/drug effects/radiation effects MH - Disease Models, Animal MH - *Electronics MH - Eye Proteins/*pharmacology MH - Female MH - Fibroblast Growth Factor 2/*pharmacology MH - Light/*adverse effects MH - Nerve Growth Factors/*pharmacology MH - Neuroprotective Agents/*pharmacology MH - Quinoxalines/*pharmacology MH - Rats, Sprague-Dawley MH - Retinal Cone Photoreceptor Cells/drug effects/*pathology/*radiation effects MH - Serpins/*pharmacology MH - Time Factors MH - Tomography, Optical Coherence PMC - PMC4252057 COIS- Competing Interests: Funding for the present study was provided by Allergan Sales LLC. The authors confirm that this funding does not alter their adherence to PLOS ONE policies on sharing data and materials. The authors also confirm that the fact that one of the coauthors (Larry A. Wheeler) is employed by a commercial company (Zeteo Drug Discovery LLC, Irvine, California, USA), does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials. EDAT- 2014/12/03 06:00 MHDA- 2015/07/29 06:00 PMCR- 2014/12/02 CRDT- 2014/12/03 06:00 PHST- 2014/09/07 00:00 [received] PHST- 2014/10/30 00:00 [accepted] PHST- 2014/12/03 06:00 [entrez] PHST- 2014/12/03 06:00 [pubmed] PHST- 2015/07/29 06:00 [medline] PHST- 2014/12/02 00:00 [pmc-release] AID - PONE-D-14-40015 [pii] AID - 10.1371/journal.pone.0113798 [doi] PST - epublish SO - PLoS One. 2014 Dec 2;9(12):e113798. doi: 10.1371/journal.pone.0113798. eCollection 2014.