Experimental and clinical evidence of neuroprotection by nerve growth factor eye drops: Implications for glaucoma.
Elevated intraocular pressure (IOP) in glaucoma causes loss of retinal ganglion cells (RGCs) and damage to the optic nerve. Although IOP is controlled pharmacologically, no treatment is available to restore retinal and optic nerve function. We evaluated the effects of NGF eye drops in a rat model of glaucoma. We also treated 3 patients with progressive visual field defects despite IOP control. Glaucoma was induced in rats through injection of hypertonic saline into the episcleral vein. Initially, 2 doses of NGF (100 and 200 mug/mL) were tested on 24 rats, and the higher dose was found to be more effective. Glaucoma was then induced in an additional 36 rats: half untreated and half treated with 200 mug/mL NGF QID for 7 weeks. Apoptosis/survival of RGCs was evaluated by histological, biochemical, and molecular analysis. Three patients with advanced glaucoma underwent psychofunctional and electrofunctional tests at baseline, after 3 months of NGF eye drops, and after 3 months of follow-up. Seven weeks of elevated IOP caused RGC degeneration resulting in 40% cell death. Significantly less RGC loss was observed with NGF treatment (2,530 +/- 121 vs. 1,850 +/- 156 RGCs/mm(2)) associated with inhibition of cell death by apoptosis. Patients treated with NGF demonstrated long lasting improvements in visual field, optic nerve function, contrast sensitivity, and visual acuity. NGF exerted neuroprotective effects, inhibiting apoptosis of RGCs in animals with glaucoma. In 3 patients with advanced glaucoma, treatment with topical NGF improved all parameters of visual function. These results may open therapeutic perspectives for glaucoma and other neurodegenerative diseases.
Lambiase
Alessandro
A
Centro Integrato di Ricerca, Department of Ophthalmology, University of Rome Campus Bio-Medico and Fondazione Alberto Sordi, 00128 Rome, Italy.
Aloe
Luigi
L
Centofanti
Marco
M
Parisi
Vincenzo
V
Báo
Sonia Nair
SN
Mantelli
Flavio
F
Colafrancesco
Valieria
V
Manni
Gian Luca
GL
Bucci
Massimo Gilberto
MG
Bonini
Stefano
S
Levi-Montalcini
Rita
R
D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D015350:Contrast Sensitivity / Q000187:drug effects; D004195:Disease Models, Animal; D005260:Female; D005901:Glaucoma / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D007429:Intraocular Pressure / Q000187:drug effects; D008297:Male; D051379:Mice; D008875:Middle Aged; D020932:Nerve Growth Factor / Q000008:administration & dosage*; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D009883:Ophthalmic Solutions; D009900:Optic Nerve / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000473:pathology; D014792:Visual Acuity / Q000187:drug effects; D014794:Visual Fields / Q000187:drug effects
D018696:Neuroprotective Agents; D009883:Ophthalmic Solutions; D020932:Nerve Growth Factor