Ocular application of nerve growth factor protects degenerating retinal ganglion cells in a rat model of glaucoma.
OBJECTIVE
Elevated intraocular pressure is a crucial pathologic event for the development of glaucoma (GL). We have reported that nerve growth factor (NGF) reaches retinal cells and the optic nerve (ON) when applied to the eye. Whether ocular application of NGF prevents or reduces damage to retinal ganglion cell (RGC) is not known.


METHODS
GL was induced in adult rats by the injection of hypertonic saline into the episcleral vein of the right eye and the left eye used as control. Rats were then treated daily with ocular application of NGF or vehicle solution for 7 weeks. Retinal and ON tissues were then used for structural, immunohistochemical, and biochemical studies.


RESULTS
The injection of hypertonic saline into the episcleral vein led to progressive degeneration of RGCs, with the loss of nearly 40% of these cells after 7 weeks of treatment. This cellular loss is associated with the downregulation of NGF and NGF-receptor expression in the retina and ON of the glaucomatous eye and ocular treatment with NGF significantly reduced the deficit induced by GL.


CONCLUSIONS
These findings indicate that NGF can exert protective action on RGC degeneration occurring in glaucomatous retina. We suggest that ocular NGF treatment might be a suitable pharmacologic approach to investigate protective mechanisms of degenerating RGCs.
Colafrancesco
Valeria
V
Department of Ophthalmology, IRCCS, G.B. Bietti Eye Foundation, Rome, Italy.
Parisi
Vincenzo
V
Sposato
Valentina
V
Rossi
Simona
S
Russo
Matteo Antonio
MA
Coassin
Marco
M
Lambiase
Alessandro
A
Aloe
Luigi
L
D000287:Administration, Topical; D000818:Animals; D015153:Blotting, Western; D002452:Cell Count; D004195:Disease Models, Animal; D005901:Glaucoma / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D007150:Immunohistochemistry; D007429:Intraocular Pressure; D008297:Male; D009410:Nerve Degeneration; D020932:Nerve Growth Factor / Q000008:administration & dosage*; D009883:Ophthalmic Solutions / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D020800:Receptor, Nerve Growth Factor / Q000378:metabolism; D020917:Receptor, trkA / Q000378:metabolism; D012162:Retinal Degeneration / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D014065:Tonometry, Ocular
D009883:Ophthalmic Solutions; D020800:Receptor, Nerve Growth Factor; D020932:Nerve Growth Factor; D020917:Receptor, trkA