Estrogen protects the inner retina from apoptosis and ischemia-induced loss of Vesl-1L/Homer 1c immunoreactive synaptic connections.
OBJECTIVE
Protective effects of estrogen on nerve cells including retinal neurons have been described previously. However, subcellular effects on synaptic connectivity in mild ischemia more closely resembling ischemic conditions found in diabetic or sickle cell retinopathy and stenosis of the carotid artery have not been identified. The present study quantitatively analyzed effects of estrogen administration on synaptic connections of neurons in the ganglion cell layer (GCL) of the retina.


METHODS
Staining of Vesl-1L/Homer 1c (V-1L) immunoreactivity and TUNEL cytochemistry were used to quantify neuroprotective effects at the synaptic level in a model of mild retinal ischemia induced by temporary middle cerebral artery occlusion in the adult rat.


RESULTS
V-1L immunoreactivity was found in both synaptic layers, postsynaptic to glutamatergic ribbon synapses. Mild retinal ischemia led to a significantly higher percentage reduction in the number of V-1L-positive synapses in the inner plexiform layer (IPL) compared with the percentage of TUNEL-positive apoptotic neurons in the GCL. Estrogen prevented ischemia-induced loss of V-1L-immunoreactive synapses in the IPL and apoptosis of cells in the GCL.


CONCLUSIONS
Immunoreactivity for V-1L can be used as a synaptic marker for early changes before more severe neurodegenerative events. The present results suggest that estrogen protects neurons in the GCL including RGCs from both apoptosis and early changes in synaptic connections associated with ischemia and potentially preceding apoptosis.
Kaja
Simon
S
University of North Texas Health Science Center at Fort Worth, Department of Pharmacology and Neuroscience, Fort Worth, Texas 76107-2699, USA.
Yang
Shao-Hua
SH
Wei
Jiao
J
Fujitani
Kazuko
K
Liu
Ran
R
Brun-Zinkernagel
Anne-Marie
AM
Simpkins
James W
JW
Inokuchi
Kaoru
K
Koulen
Peter
P
D000818:Animals; D017209:Apoptosis; D015415:Biomarkers; D002352:Carrier Proteins / Q000378:metabolism*; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D000072233:Homer Scaffolding Proteins; D020287:In Situ Nick-End Labeling; D007511:Ischemia / Q000378:metabolism / Q000517:prevention & control*; D016253:Microscopy, Immunoelectron; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012164:Retinal Diseases / Q000378:metabolism / Q000517:prevention & control*; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000473:pathology; D012171:Retinal Vessels / Q000187:drug effects / Q000378:metabolism; D013569:Synapses / Q000378:metabolism*
D015415:Biomarkers; D002352:Carrier Proteins; D004967:Estrogens; D000072233:Homer Scaffolding Proteins; D009479:Neuropeptides; D018696:Neuroprotective Agents