Topical Brimonidine or Intravitreal BDNF, CNTF, or bFGF Protect Cones Against Phototoxicity

Francisco J Valiente-Soriano; Arturo Ortín-Martínez; Johnny Di Pierdomenico; Diego García-Ayuso; Alejandro Gallego-Ortega; Juan A Miralles de Imperial-Ollero; Manuel Jiménez-López; María Paz Villegas-Pérez; Larry A Wheeler; Manuel Vidal-Sanz

doi:10.1167/tvst.8.6.36

Topical Brimonidine or Intravitreal BDNF, CNTF, or bFGF Protect Cones Against Phototoxicity

Transl Vis Sci Technol. 2019 Dec 16;8(6):36. doi: 10.1167/tvst.8.6.36. eCollection 2019 Nov.

Affiliations

¹ Departamento de Oftalmología, Facultad de Medicina, Universidad de Murcia, e Instituto Murciano de Investigación Biosanitaria Virgen de la Arrixaca (IMIB-Arrixaca), Murcia, Spain.
² Present Address: Donald K. Johnson Eye Institute, Krembil Research Institute, University Health Network, Toronto, ON, Canada.
³ Ophthalmology and Visual Science, University of Utah Health Sciences Center, Salt Lake City, UT, USA.

Abstract

Purpose: To develop a focal photoreceptor degeneration model by blue light-emitting diode (LED)-induced phototoxicity (LIP) and investigate the protective effects of topical brimonidine (BMD) or intravitreal brain-derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF), or basic fibroblast growth factor (bFGF).

Methods: In anesthetized, dark-adapted, adult female Swiss mice, the left eye was dilated and exposed to blue light (10 seconds, 200 lux). After LIP, full-field electroretinograms (ERG) and spectral-domain optical coherence tomography (SD-OCT) were obtained longitudinally, and reactive-Iba-1⁺monocytic cells, TUNEL⁺ cells and S-opsin⁺ cone outer segments were examined up to 7 days. Left eyes were treated topically with BMD (1%) or vehicle, before or right after LIP, or intravitreally with BDNF (2.5 μg), CNTF (0.2 μg), bFGF (0.5 μg), or corresponding vehicle right after LIP. At 7 days, S-opsin⁺ cone outer segments were counted within predetermined fixed-size areas (PFA) centered on the lesion in both flattened retinas.

Results: SD-OCT showed a circular region in the superior-temporal left retina with progressive thinning (207.9 ± 5.6 μm to 160.7 ± 6.8 μm [7 days], n = 8), increasing TUNEL⁺ cells (peak at 3 days), decreasing S-opsin⁺ cone outer segments, and strong microglia activation. ERGs were normal by 3 days. Total S-opsin⁺ cones in the PFA for LIP-treated and fellow-retinas were 2330 ± 262 and 5601 ± 583 (n = 8), respectively. All neuroprotectants (n = 7-11), including topical BMD pre- or post-LIP, or intravitreal BDNF, CNTF, and bFGF, showed significantly greater S-opsin⁺ cone survival than their corresponding vehicle-treated groups.

Conclusions: LIP is a reliable, quantifiable focal photoreceptor degeneration model. Topical BMD or intravitreal BDNF, CNTF, or bFGF protect against LIP-induced cone-photoreceptor loss.

Translational relevance: Topical BMD or intravitreal BDNF, CNTF, or bFGF protect cones against phototoxicity.

Keywords: BDNF; Brimonidine; CNTF; SD-OCT; alpha-2-adrenergic agonist; bFGF; cone photoreceptors; light induced phototoxicity; microglia; neuroprotection.