Biomedical subjects

G J Mahon

Publications and source records attributed to G J Mahon.

5 recordsLinked to original sources

PubMed2004

Chloroquine causes lysosomal dysfunction in neural retina and RPE: implications for retinopathy.

Chronic use of chloroquine has been shown to induce numerous pathophysiological defects in the retina. This drug has the ability to alter pH of intracellular compartments and lysosomal function of the retinal pigment epithelium (RPE) and retinal neurons may constitute the basis of chloroquine retinopathy. The aim of the current study was to investigate pathogenic alterations in retinal cells continuously exposed to chloroquine using appropriate in vivo and in vitro models. Male hooded Lister rats were implanted with osmotic mini pumps which released chloroquine continuously over a period of seven days. The eyes were processed for electron microscopy and ultrastructural abnormalities determined in the neural retina and quantified using stereology in the retinal pigment epithelium (RPE). RPE were also exposed to chloroquine in vitro and lysosomal pH changes were investigated using a pH sensitive probe. Degradative capacity was also analysed using FITC labeled rod outer segments (ROS). Chloroquine-treated animals displayed several ultrastructural abnormalities including numerous membranous cytoplasmic bodies (MCBs) in retinal neurons. Cone photoreceptors displayed numerous MCBs although rods did not. The RPE of the treated groups all showed significantly higher numbers of lysosomal associated organelles (LAO) than the control group (p < 0.001). The in vitro experiments demonstrated chloroquine-mediated rises in lysosomal pH and an increase in lysosome/phagosome accumulation of ROS in the chloroquine treated group (p < 0.01). The current study demonstrates that chloroquine disrupts lysosomal function in retinal neurons and RPE. The evidence presented provides a clear pathogenic basis for the functional defects experienced by patients with chloroquine retinopathy.

Animals↗

PubMed1993

Ultrastructural findings in solar retinopathy.

This study documents the ultrastructural findings in a case of solar retinopathy, 6 days after sungazing. A malignant melanoma of the choroid was diagnosed in a 65-year-old man. On fundoscopy, the macula was normal. The patient agreed to stare at the sun prior to enucleation. A typical solar retinopathy developed, characterised by a small, reddish, sharply circumscribed depression in the foveal area. Structural examination of the fovea and parafovea revealed a spectrum of cone and rod outer segment changes including vesiculation and fragmentation of the photoreceptor lamellae and the presence of discrete 100-120 nm whorls within the disc membranes. Many photoreceptor cells, particularly the parafoveal rods, also demonstrated mitochondrial swelling and nuclear pyknosis. Scattered retinal pigment epithelial cells in the fovea and parafovea showed a degeneration characterised by loss of plasma membrane specialisations, swelling of the smooth endoplasmic reticulum and changes in the fine structure of the lipofuscin granules. The good visual prognosis in solar retinopathy was attributed to the resistance of the foveal cone cells to photochemical damage.

Aged↗

PubMed1993

Ocular siderosis.

The authors report their experience in the management of 8 patients with ocular siderosis due to a retained intraocular foreign body (IOFB). All patients were male, aged between 19 and 39 years. Seven had a definite history of trauma; 3 had presented at the time of injury to a casualty department, and the diagnosis had been missed. The interval between injury and diagnosis ranged from 2 to 24 months. IOFB removal was performed in 7 patients: through a sclerotomy and magnet or foreign body forceps in 4 eyes and via a pars plana vitrectomy and intraocular foreign body forceps in 3 eyes. Cataract extraction was performed in 4 patients. Histological examination of specimens removed at the time of surgery showed iron deposition in the conjunctiva, anterior lens capsule and pars plana. Transmission electron microscope X-ray microanalysis showed that iron was contained in siderosomes, intracytoplasmic membrane-bound dense bodies. Final visual acuity was 6/12 or better in 6 patients and reduced to light perception in the remaining 2 due to proliferative vitreoretinopathy.

Adult↗

PubMed1992

Late ultrastructural changes in the retina of the rat following low-dose X-irradiation.

This study describes ultrastructural changes in the pigmented hooded Lister rat retina, 3-12 months following X-irradiation with single doses of between 200 and 2000 cGy. The extreme radiosensitivity of the photoreceptor cells was underlined by the continued manifestation of fine structural changes and cell death up to 6 months post-radiation in animals receiving doses above 500 cGy. The retinal pigment epithelial (RPE) cells were more radioresistant than photoreceptors and RPE cell loss was only observed at doses of more than 1500 cGy. One year after irradiation with 1500 cGy the retinal vasculature showed capillary occlusion with some evidence of recanalisation. Telangiectasia was observed in the large retinal veins. Although the inner retinal neurones and glial cells showed no evidence of direct radiation damage, the nerve fibre layer adjacent to occluded retinal vessels demonstrated ultrastructural evidence of ischaemic neuropathy and retinal oedema. At doses above 1500 cGy the choriocapillaris showed platelet aggregation and capillary loss.

Animals↗

PubMed1989

Early ultrastructural changes after low-dose X-irradiation in the retina of the rat.

In this study Lister rats were given doses of X-rays ranging from 200-2,000 Rads to the retina of one eye, sacrificed at various time intervals between one hour and one month later and the irradiated eye processed for electron microscopy. The rod photoreceptor cells were by far the most radiosensitive cells in the retina, their outer segments showing distinctive membrane damage at one hour after 200 Rads of X-rays. Photoreceptor cell death was not seen at doses less than 1,000 Rads in the time period of the experiment. The retinal pigment epithelial (RPE) cells showed damage in the form of mitochondrial swelling but only in doses over 500 Rads. Retinal pigment epithelial cell loss did not occur under 2,000 Rads. The inner retinal neurones, glial elements and the retinal vasculature did not show any ill effects in the time period of this study.

Animals↗