Experimental Investigation of the Morphogenesis of Chloroquine Retinopathy

Meier‐Ruge, W.

doi:10.1001/archopht.1965.00970030542017

Cited by 53 publications

(14 citation statements)

References 30 publications

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“…Chloroquine is said to accumulate in the pigment epithelium and in the receptor cells, and similarly in degenerative myopia the pathological process appears to start * In myopia the second and fourth of these factors are suspect. Certainly in chloroquine retinopathy, where the electrical findings are similar to those in myopia, the pigment epithelium is known to be involved (Kolb, 1965;Meier-Ruge, 1965). in the choroid and pigment epithelium with early involvement of the receptor cells.…”

Section: Discussionmentioning

confidence: 99%

Electrical activity of the eye in high myopia.

Blach¹,

Jay²,

Kolb³

1966

British Journal of Ophthalmology

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IT IS generally agreed that simple myopia and degenerative myopia are separate conditions, the former being a normal chance variant in the biological series which includes emmetropia and hypermetropia (Duke-Elder, 1949) and the latter a pathological condition. Degenerative myopia in its advanced stage consists of an association of defects: a highly myopic refraction, chorio-retinal degeneration and atrophy, thinning of the posterior sclera, and an increased axial length of the eye. Additional defects, such as cupuliform cataract, glaucoma, and retinal detachment, are relatively common in patients with degenerative myopia, and a hereditary element is often present. In the investigation here reported the function of eyes with degenerative myopia has been studied using electroretinography and electro-oculography.Although degenerative myopia may be congenital, it usually takes many years to develop. In its early stages a myopic refraction, straight temporal vessels, and a temporal crescent at the optic disc may be the only physical signs, and these cannot be distinguished from cases of simple myopia (Blach, Jay, and MacFaul, 1965). It is hoped that the electrical tests described here may prove to be of some diagnostic and prognostic value, and be of some help in pointing to the primary defect in degenerative myopia.Review Karpe (1945) performed ERGs on four eyes with high myopia; in three the ERG was definitely subnormal, while in the last it was probably subnormal. Fran9ois and de Rouck (1954) studied the ERG in patients with both simple and degenerative myopia; those with simple myopia had normal ERGs, while in 75 per cent. of those with high myopia the b waves were depressed and the a waves varied from strongly positive to completely absent. They claimed that the ERG changes preceded the ophthalmoscopic changes in degenerative myopia, although they classified degenerative myopia by the fundus changes. They found no correlation between the amplitude of the b wave and the degree of myopia. From the changes occurring in the b waves, they argued that the retina rather than the choroid was primarily involved in this disease. Franceschetti, Dieterle, and Schwarz (1960) investigating fourteen cases of uniocular myopia, found that the b waves were reduced in the scotopic ERG and that this reduction was related to the degree of myopia. Jayle and Boyer (1960) found that myopic patients with good visual function had normal ERGs, while those with poor visual function had subnormal ERGs; they suggested that the photopic system was involved before the scotopic system. Ponte (1962) found that in simple myopia the mean amplitude of the b wave was slightly reduced, while in severe myopia the ERG was considerably affected, the most frequent finding being a subnormal ERG of negative type.Franqois, Verriest, and de Rouck (1956) examined four patients with high myopia and pronounced choroidal changes and found that the resting potential level was normal. On the other hand, Arden, Barrada, and Kelsey (1962) performed EOGs on a number...

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Section: Discussionmentioning

confidence: 99%

Electrical activity of the eye in high myopia.

Blach¹,

Jay²,

Kolb³

1966

British Journal of Ophthalmology

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“…Chronic treatment of primates with chloroquine led to lipid accumulations in the RPE, a thickened basement membrane with collagen fibrils, and increased choroidal macrophages (Rosenthal et al, 1978). In cats, extended chloroquine treatment led to RPE hypertrophy followed by loss of photoreceptors (Meier-Ruge, 1965). In rats, chloroquine led to an accumulation of lysosomal-associated organelles in RPE cells and to lipid deposits throughout Bruch’s membrane (Ivanina et al, 1983; Peters et al, 2006).…”

Section: Chronic Retinal Degenerations Ion Transport Autophagy Amentioning

confidence: 99%

Approaches for detecting lysosomal alkalinization and impaired degradation in fresh and cultured RPE cells: Evidence for a role in retinal degenerations

Guha

Coffey

et al. 2014

Experimental Eye Research

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Lysosomes contribute to a multitude of cellular processes, and the pH of the lysosomal lumen plays a central mechanistic role in many of these functions. In addition to controlling the rate of enzymatic degradation for material delivered through autophagic or phagocytotic pathways, lysosomal pH regulates events such as lysosomal fusion with autophagosomes and the release of lysosomal calcium into the cytoplasm. Disruption of either the steady state lysosomal pH or of the regulated manipulations to lysosomal pH may be pathological. For example, chloroquine elevates the lysosomal pH of retinal pigmented epithelial (RPE) cells and triggers a retinopathy characterized by the accumulation of lipofuscin-like material in both humans and animals. Compensatory responses to restore lysosomal pH are observed; new data illustrate that chronic chloroquine treatment increases mRNA expression of the lysosomal/autophagy master transcription factor TFEB and of the vesicular proton pump vHATPase in the RPE/choroid of mice. An elevated lysosomal pH with upregulation of TFEB and vHATPase resembles the pathology in fibroblasts of patients with mutant presenilin 1 (PS1), suggesting a common link between age-related macular degeneration (AMD) and Alzheimer’s disease. While the absolute rise in pH is often small, elevations of only a few tenths of a pH unit can have a major impact on both lysosomal function and the accumulation of waste over decades. Accurate measurement of lysosomal pH can be complex, and imprecise measurements have clouded the field. Protocols to optimize pH measurement from fresh and cultured cells are discussed, and indirect measurements to confirm changes in lysosomal pH and degradative capacity are addressed. The ability of reacidifying treatments to restore degradative function confirms the central role of lysosomal pH in these functions and identifies potential approaches to treat diseases of accumulation like AMD and Alzheimer’s disease. In summary, various approaches to determine lysosomal pH in fresh and cultured cells, as well as the potential to restore pH levels to an optimal range, can help identify and repair pathologies associated with lysosomal defects in RPE cells and perhaps also suggest new approaches to treat lysosomal storage diseases throughout the body.

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“…The chloroquinone retinopathy is characterized by a toxic edema of the pigment epithelium [76,77] ( fig. 13 ).…”

Section: Applications Of Enzyme Histochemistry In Experimental Pathologymentioning

confidence: 99%

Current Concepts of Enzyme Histochemistry in Modern Pathology

Meier‐Ruge

Bruder²

2008

Pathobiology

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Enzyme histochemistry serves as a link between biochemistry and morphology. It is based on metabolization of a substrate provided to a tissue enzyme in its orthotopic localization. Visualization is accomplished with an insoluble dye product. It is a sensitive dynamic technique that mirrors even early metabolic imbalance of a pathological tissue lesion, combined with the advantage of histotopographic enzyme localization. With the advent of immunohistochemistry and DNA-oriented molecular pathology techniques, the potential of enzyme histochemistry currently tends to be underrecognized. This review aims to draw attention to the broad range of applications of this simple, rapid and inexpensive method. Alkaline phosphatase represents tissue barrier functions in brain capillaries, duodenal enterocyte and proximal kidney tubule brush borders. Decrease in enzyme histochemical alkaline phosphatase activity indicates serious functional impairment. Enzyme histochemical increase in lysosomal acid phosphatase activity is an early marker of ischemic tissue lesions. Over the last four decades, acetylcholinesterase enzyme histochemistry has proven to be the gold standard for the diagnosis of Hirschsprung disease and is one of the most commonly applied enzyme histochemical methods today. Chloroacetate esterase and tartrate-resistant phosphatase are both resistant to formalin fixation, EDTA decalcification and paraffin embedding. Early enzyme histochemical insight into development of a pathologic tissue lesion and evaluation of function and vitality of tissue enhance our understanding of the pathophysiology of diseases. In this process, enzyme histochemistry constitutes a valuable complement to conventional histology, immunohistochemistry and molecular pathology for both diagnostic and experimental pathology.

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Experimental Investigation of the Morphogenesis of Chloroquine Retinopathy

Cited by 53 publications

References 30 publications

Electrical activity of the eye in high myopia.

Electrical activity of the eye in high myopia.

Approaches for detecting lysosomal alkalinization and impaired degradation in fresh and cultured RPE cells: Evidence for a role in retinal degenerations

Current Concepts of Enzyme Histochemistry in Modern Pathology

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