Neuroprotective effect of intravitreal triamcinolone acetonide against photoreceptor apoptosis in a rabbit model of subretinal hemorrhage.
OBJECTIVE
To study photoreceptor apoptosis and iron migration as mechanisms of retinotoxicity in a rabbit model of subretinal hemorrhage (SRH) and to assess intravitreal triamcinolone acetonide (IVTA) for anti-apoptotic and neuroprotective effects.


METHODS
In adult rabbits, eyes were studied histologically after subretinal injection of autologous blood. For comparisons of control eyes with eyes injected with 2 mg IVTA, morphometric analysis was performed with light microscopy, whereas apoptosis was quantified with terminal dUTP nick end labeling (TUNEL) and fluorescence microscopy. Localization of retinal iron was assessed with Perls' stain.


RESULTS
Photoreceptor degeneration was initiated 48 hours after exposure to subretinal blood and progressed over 7 days. Increased TUNEL positivity demonstrating apoptotic cell death was associated with SRH and photoreceptor loss. VIP-Perls staining demonstrated iron in the photoreceptor layer and retinal pigment epithelium that correlated with photoreceptor degeneration. Treatment with IVTA enhanced photoreceptor cell survival by 11% at 48 hours and by 45% at 72 hours (P = 0.01) and reduced photoreceptor apoptosis ratios by 25% at 48 hours (P = 0.006).


CONCLUSIONS
Photoreceptor toxicity caused by SRH occurs at least in part by apoptosis and is associated with iron migration to the photoreceptor layer. Treatment with IVTA reduced photoreceptor loss and apoptosis, indicating a neuroprotective action. Therapies to target SRH may augment anti-VEGF treatments in exudative age-related macular degeneration and other diseases of choroidal neovascularization.
Bhisitkul
Robert B
RB
Department of Ophthalmology, Epidemiology and Biostatistics Division, University of California at San Francisco, School of Medicine, San Francisco, California, USA.
Winn
Bryan J
BJ
Lee
On-Tat
OT
Wong
Joshua
J
Pereira
Daniel de Souza
Dde S
Porco
Travis C
TC
He
Xining
X
Hahn
Paul
P
Dunaief
Joshua L
JL
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D004195:Disease Models, Animal; D005260:Female; D007501:Iron / Q000378:metabolism; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D010786:Photoreceptor Cells / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D011430:Propoxycaine / Q000494:pharmacology; D011680:Pupil / Q000187:drug effects / Q000502:physiology; D011817:Rabbits; D012166:Retinal Hemorrhage / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D014222:Triamcinolone Acetonide / Q000008:administration & dosage / Q000627:therapeutic use*; D014822:Vitreous Body / Q000187:drug effects / Q000503:physiopathology*
D018696:Neuroprotective Agents; C005717:proxymetacaine; D007501:Iron; D011430:Propoxycaine; D014222:Triamcinolone Acetonide