Experimental Study of the Retinal Toxicity of Hemoglobinic Iron

Doly, M.; Bonhomme, Brigitte; Vennat, Jean-Claude

doi:10.1159/000265409

Cited by 37 publications

(14 citation statements)

References 5 publications

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“…Iron retained in the eye as a foreign body or injected into the vitreous causes photoreceptor degeneration, demonstrating that iron overload is toxic to photoreceptors (1)(2)(3). A comparison of postmortem retinas from age-related macular degeneration (AMD) and normal donors documented increased iron within the retinal pigment epithelium (RPE) (4), a cellular monolayer forming the blood-retinal barrier and nourishing photoreceptors.…”

mentioning

confidence: 99%

Disruption of ceruloplasmin and hephaestin in mice causes retinal iron overload and retinal degeneration with features of age-related macular degeneration

Hahn

Qian

Dentchev

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

245

234

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Mechanisms of brain and retinal iron homeostasis have become subjects of increased interest after the discovery of elevated iron levels in brains of patients with Alzheimer's disease and retinas of patients with age-related macular degeneration. To determine whether the ferroxidase ceruloplasmin (Cp) and its homolog hephaestin (Heph) are important for retinal iron homeostasis, we studied retinas from mice deficient in Cp and͞or Heph. In normal mice, Cp and Heph localize to Mü ller glia and retinal pigment epithelium, a blood-brain barrier. Mice deficient in both Cp and Heph, but not each individually, had a striking, age-dependent increase in retinal pigment epithelium and retinal iron. The iron storage protein ferritin was also increased in Cp؊͞؊Heph؊͞Y retinas. After retinal iron levels had increased, Cp؊͞؊Heph؊͞Y mice had age-dependent retinal pigment epithelium hypertrophy, hyperplasia and death, photoreceptor degeneration, and subretinal neovascularization, providing a model of some features of the human retinal diseases aceruloplasminemia and age-related macular degeneration. This pathology indicates that Cp and Heph are critical for CNS iron homeostasis and that loss of Cp and Heph in the mouse leads to age-dependent retinal neurodegeneration, providing a model that can be used to test the therapeutic efficacy of iron chelators and antiangiogenic agents.

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mentioning

confidence: 99%

Disruption of ceruloplasmin and hephaestin in mice causes retinal iron overload and retinal degeneration with features of age-related macular degeneration

Hahn

Qian

Dentchev

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

245

234

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“…In non-hemorrhagic lesions, alterations are readily apparent to Bruch's membrane as basement membrane matrix hypertrophy (11,12,21), suggesting that pathology is mediated by abnormal proliferating and transformed RPE cells (22). Also, large field photoreceptor losses may be related to free radical production by blood break down products (23,24). When trauma was more severe, more extensive fibrosis and hyperplastic neovascularization (11,12,21) occurred.…”

Section: Discussionmentioning

confidence: 99%

Significance of retinal laser lesion location and subretinal hemorrhage in bridging choroidal neovascular complexes

et al. 2003

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Purpose:To determine funduscopic criteria that will help predict when bridging choroidal neovascular (CNV) complexes will develop after laser retinal trauma and to define early preventive treatment targets. Methods: Ten rhesus monkeys were used and retinal lesions were produced by Nd:YAG exposures (20ns, 1-2mJ, 1064nm, min. spot size) simulating human accidental laser trauma to the central fundus. Funduscopy, fluorescein/ICG angiography, and optical coherence tomography (OCT) were conducted at day 1, 4, and 14, and at 2 and 4 months, after which animals were terminated for histologic evaluation. Predisposition for bridging fibrovascular complexes was evaluated for single hemorrhagic lesions, two small lesions showing coalescing hemorrhages, and multiple lesions involved with large field subretinal and vitreous hemorrhages. Results: All single lesions with confined subretinal hemorrhages showed elevated CNVs. All lesion sets that showed small coalescing subretinal hemorrhages formed bridging CNV scars. No bridging CNVs occurred in lesion sets involving a vitreous hemorrhage adjacent to a confined but small subretinal hemorrhage. Complex CNV formation occurred in large field subretinal hemorrhages involving multiple laser lesions. Extensive secondary photoreceptor losses occurred in large and confined hemorrhage and CNV zones. Conclusions: Trauma presenting with evidence of coalescing and confined subretinal hemorrhages between two adjacent lesions has a high chance of forming choroidal neovascular bridge complexes between the involved lesions. Release of subretinal blood through a vitreous hemorrhage reduced the chances of cross-bridging CNV formation, except for largefield subretinal hemorrhages. CNV formation may be related to the long residence time, break down products, and clearance processes of extravasated blood. Retinal detachment complications produced by the hemorrhage may further contribute to CNVs. Removal of trapped blood and curtailing angiogenesis and cellular proliferation may be helpful treatment strategies.

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“…The E R G is considered a sensitive tech nique by which to establish the functional consequences o f toxic retinal agents [11], and it has been used to study the effect of vitreous hemorrhage and hemoglobinic iron on the retina [12,13].…”

Section: Discussionmentioning

confidence: 99%

Tolerance of Intravitreous lnterleukin-1 β in the Treatment of Experimental Vitreous Hemorrhage

Pastor

González²,

Ja³

et al. 1995

Ophthalmic Res

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We investigated the tolerance of human recombinant interleukin-1β (IL-1β) injected intravitreously and its putative role in the clearance of experimental vitreous hemorrhages. Three groups of 10 pigmented rabbits each were injected intravitreously with 0.1 ml autologous whole blood. Mean fundus revisualization times after blood clouding were as follows: group 1 (controls, blood injection only), 5.3 weeks; group 2 (100 units of IL-1β injected intravitreously 7 days after blood injection), 3.3 weeks; group 3 (1,000 units of IL-1β injected intravitreously 7 days after blood injection), 3.2 weeks. Group 4 (10 rabbits) was injected only with 1,000 units of IL-1β. Clinical examinations showed a transient mild inflammatory reaction in group 2 and a transient severe reaction in groups 3 and 4. Vitreous opacities, a whitish retinal reaction and vascular changes were seen in group 4. Electroretinography did not show a b-wave decrease in any group. These results suggest that low concentrations of IL-1β may be useful for nonsurgical treatment of human vitreous hemorrhage.

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Experimental Study of the Retinal Toxicity of Hemoglobinic Iron

Cited by 37 publications

References 5 publications

Disruption of ceruloplasmin and hephaestin in mice causes retinal iron overload and retinal degeneration with features of age-related macular degeneration

Disruption of ceruloplasmin and hephaestin in mice causes retinal iron overload and retinal degeneration with features of age-related macular degeneration

Significance of retinal laser lesion location and subretinal hemorrhage in bridging choroidal neovascular complexes

Tolerance of Intravitreous lnterleukin-1 β in the Treatment of Experimental Vitreous Hemorrhage

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