The developing mammalian retina is partially protected from gentamicin toxicity.
Gentamicin retinal toxicity was tested in numerous studies on adult animal models, but not in the developing retina. Since differentiating cells and developing tissues may exhibit different degrees of sensitivity to toxic drugs, we aimed here to test the susceptibility of the developing mammalian retina to the toxic action of gentamicin. Gentamicin was injected in the right eye of newborn rabbits, aged 11-38 days. The left eye of each rabbit was injected with saline. Eight weeks after injection, electroretinographic (ERG) responses were recorded in the dark- and light-adapted states. The rabbits were then sacrificed, and the retinas were prepared for morphological examination and immunostaining for Glial Fibrillary Acidic Protein (GFAP) and Protein Kinase C (PKC). The ERG responses demonstrated practically no functional damage to the retina of rabbits injected at postnatal age of 11 and 13 days, and a gradually increasing severity of functional damage with increasing postnatal age of intravitreal gentamicin injection. The histopathological studies yielded similar results. GFAP immunoreactivity showed staining in Müller cells only in retinas that exhibited functional and structural damage. PKC immunoreactivity indicated lesser damage to the rod-bipolar cells compared to the photoreceptors. The ERG data and morphological observations suggest that processes involved in development of the rabbit retina, such as outer segment elongation may provide partial or even complete protection to the retina from toxic insults such as a single dose of gentamicin.
Soudry
Shiri
S
Department of Ophthalmology, Tel Aviv Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Zemel
Esther
E
Loewenstein
Anat
A
Perlman
Ido
I
D000221:Adaptation, Ocular / Q000502:physiology; D000367:Age Factors; D000375:Aging / Q000502:physiology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000633:toxicity*; D004596:Electroretinography / Q000187:drug effects; D005839:Gentamicins / Q000633:toxicity*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007267:Injections; D011493:Protein Kinase C / Q000378:metabolism; D011817:Rabbits; D012160:Retina / Q000187:drug effects* / Q000254:growth & development / Q000473:pathology / Q000503:physiopathology; D014822:Vitreous Body
D000900:Anti-Bacterial Agents; D005839:Gentamicins; D005904:Glial Fibrillary Acidic Protein; D011493:Protein Kinase C