+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Retinal function and morphology in monkeys with ethambutol-induced optic neuropathy



Retinal function and morphology in monkeys with ethambutol-induced optic neuropathy



Investigative Ophthalmology and Visual Science 53(11): 7052-7062



Ethambutol-induced optic neuropathy is a well recognized adverse ocular event. However, abnormalities of the retina in this optic neuropathy are not fully understood. Therefore, the purpose of the present study was to investigate both functional and morphological alterations of the retina induced by ethambutol in monkeys. Ethambutol was orally administered to three cynomolgus monkeys, initially at 400 mg/kg/day followed by 800 mg/kg/day, for a maximum of 39 weeks. Full-field electroretinograms (ERGs) were recorded at intervals of approximately one month. The protocol included standard ERG responses to white flashes obtained under dark-adapted conditions (rod, combined rod-cone, oscillatory potentials) or with a white background (single-flash cone, 30 Hz flicker). In addition, we measured the ERG elicited with red flashes under blue background light (single-flash cone response [R/B]). All the ethambutol-treated monkeys were euthanized, and the retinae and various other nervous system tissues were examined histopathologically. No obvious changes were observed in the standard full-field ERGs. On the other hand, selective attenuation of the photopic negative response (PhNR) of the single-flash cone response (R/B) was observed in two out of three ethambutol-treated monkeys at week 22 or 28. Histopathology of these two monkeys revealed single cell necrosis of the retinal ganglion cells (RGCs), decreased RGCs in the parafovea and increased microglial cells in the nerve fiber layer in the retina, in addition to demyelination and glial reaction in the optic nerve, chiasm and tracts. The attenuated PhNR and histopathology of the retina indicated that RGCs were markedly damaged, both functionally and morphologically in monkeys with ethambutol-induced optic neuropathy. These results implied that RGCs are predominantly affected in the retina of patients with ethambutol-induced optic neuropathy.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 055545157

Download citation: RISBibTeXText

PMID: 22956619

DOI: 10.1167/iovs.12-10308


Related references

Leber's hereditary optic neuropathy masquerading as ethambutol-induced optic neuropathy in a young male. Indian Journal of Ophthalmology 54(3): 218-219, 2006

The role of copper on ethambutol's antimicrobial action and implications for ethambutol-induced optic neuropathy. Diagnostic Microbiology and Infectious Disease 30(2): 83-87, 1998

Decreased retinal nerve fibre layer thickness detected by optical coherence tomography in patients with ethambutol-induced optic neuropathy. British Journal of Ophthalmology 91(7): 895-897, 2007

Leber's hereditary optic neuropathy mutations in ethambutol-induced optic neuropathy. Journal of Neurology 250(1): 87-89, 2003

Longitudinal evaluation of visual function and structure for detection of subclinical Ethambutol-induced optic neuropathy. Plos one 14(4): E0215297, 2019

Longitudinal analysis of retinal nerve fiber layer and ganglion cell-inner plexiform layer thickness in ethambutol-induced optic neuropathy. Graefe's Archive for Clinical and Experimental Ophthalmology 253(12): 2293-2299, 2015

Visual function in recovered ethambutol optic neuropathy. Journal of Ocular Pharmacology and Therapeutics 11(3): 411-419, 1995

Early stage ethambutol optic neuropathy: retinal nerve fiber layer and optical coherence tomography. European Journal of Ophthalmology 19(3): 466-469, 2009

Hydroxycobalamin for ethambutol-induced optic neuropathy. Lancet 2(8256): 1176-1176, 1981

Present status of ethambutol-induced optic neuropathy. Chinese Journal of Ophthalmology 48(2): 184-188, 2012

Disentangling renal function in the context of irreversible ethambutol optic neuropathy. International Ophthalmology 30(6): 743-744, 2010

Ethambutol induced toxic optic neuropathy in HIV positive patients. International Journal of Ophthalmology 6(4): 542-545, 2013

Ethambutol-induced optic neuropathy and the 15257 mitochondrial DNA mutation. Investigative Ophthalmology & Visual Science 36(4): S1060, 1995

Bitemporal visual field defects in ethambutol-induced optic neuropathy. Journal of Neuro-Ophthalmology 31(2): 121-126, 2011

Bitemporal hemianopsia in a case of ethambutol-induced toxic optic neuropathy. Rinsho Ganka 52(5): 757-760, 1998