Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0086543 (cataract)
 29,165 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

With regard to diabetic retinopathy, in addition to the demonstration by the DCCT study that prevention is achieved by good metabolic control, our present knowledge on physiopathology leads us to imagine three types of possible therapeutic approach; inhibition of glucotoxicity, improvement of capillary flow, blockade of angiogenesis. 1) Inhibition of glucotoxicity Aldose reductase inhibitors can prevent cataract in diabetic or galactosemic rats. The effect of these drugs on retinopathy, evaluated in some clinical trials, remains controversial, suggesting a minor role. Aminoguanidine is an inhibitor of formation of advanced glycosylation end-products (AGE). This compound has been tested on a model of experimental retinopathy in rats. Parallel to the AGE decrease in retina, formation of microaneurysms and loss of endothelial cells in capillaries were delayed. Clinical tolerance allows human application and randomised trials will give further information on this potentially efficient drug. 2) Improvement of capillary flow This objective can be obtained by drugs inhibiting platelet aggregation or improving erythrocyte or leucocyte deformability. Clinical trials using such compounds were not very conclusive. 3) Blockade of angiogenesis Proliferation of new vessels is a rather severe stage of diabetic retinopathy. Angiogenesis is due to factors locally produced (as FGF, TGF and u-PA produced by anoxic tissues), systemic (IGF-1) or released by inflammatory reaction (IL1, TNF alpha and beta). One imagines usage of drugs which inhibit these factors and prevent angiogenesis. At the present time, two approaches have been used in proliferative retinopathy worsening despite panphotocoagulation; analogues of somatostatin and interferon alpha. The promissing results of these pilot studies have to be confirmed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Outlook for the future in the treatment of diabetic retinopathy]. 752 51

Visual deterioration is caused principally by media opacity, by retinal damage, or by disorders of the higher visual system posterior to the optic nerve. In this article, we focused on media and retinal disorders and clinically evaluated a newly developed system for visual function. The decrease in visual function in cataract is subjectively well evaluated by contrast sensitivity, but is difficult to evaluate objectively. Recently, a wavefront sensor has been developed and ocular higher-order aberration (HOA) can now be measured objectively. We studied the relationship between age and HOA by wavefront sensor and found that HOA, especially spherical aberration in the lens, increased abruptly at the presbyopic age. We also found that the against-the-rule astigmatism in the lens increased at this age. Next, we investigated monocular diplopia which was presumably caused by HOA. Nine eyes with monocular triplopia and with mild nuclear cataract showed significant increase of trefoil aberration and negative spherical aberration (p<0.001). The simulated retinal Landolt's image from these two aberrations showed a triple configuration. Thus we confirmed that triplopia is caused by the combination of trefoil aberration and negative spherical aberration in early nuclear cataract. Next, we investigated whether Area under Log Contrast Sensitivity Function (AULCSF) can be predicted by HOA and light scattering. Backward light scattering (BLS) was evaluated by Schei mpflug image and the forward light scattering (FLS) by a spot size of the Hartmann image compensated for the effect of HOA. HOA was evaluated by root mean square (RMS) value from Hartmann image in a 4 mm pupil. Multiple linear regression revealed that AULCSF could be predicted from BLS, FLS, and HOA, in which each parameter contributed to the prediction significantly (p<0.01). By using this predicted value of AULCSF, the improvement of vision after cataract surgery can be predicted in cataract complicated by retinal disease. It has been reported that by fundus camera equipped with adaptive optics (AO), which is an application of wavefront analysis, photoreceptors could be visualized 2-dimensionally. We developed a compact AO fundus camera and demonstrated that cones were separately analyzed at retinal loci 1 degree temporal to the fovea centralis when the ocular aberration was reduced to less than 0.1 microm RMS in a 6 mm pupil. We are going to use this apparatus for eyes with retinal disease. The functional evaluation of residual retinal ganglion cells (RGCs) in the retina with damage to the photoreceptors is critically important for selecting candidates for artificial retina or regenerative therapy. Transcorneal electrical stimulation (TES) of the retina via contact lens electrodes evokes phosphene and indirect pupillary reflex. The threshold current for evoking phosphene in severely degenerated retinas with visual acuity worse than counting fingers showed a wide distribution, which suggested that TES was useful to evaluate residual RGCs functionally. TES also showed a neuroprotective effect. We suggest that the activation of glial cells by TES up-regulates the production of IGF-1, which eventually protects RGCs. The peripheral retina is important for walking even though the spatial resolution is not high. We developed an apparatus to measure stereopsis in the peripheral retina using a wide screen, and evaluated the peripheral stereopsis of 12 patients after macular translocation surgery and squint surgery. All three patients who showed peripheral stereopsis had only a small amount of squint angle. This method may be useful to evaluate stereopsis in patients with a central scotoma.
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PMID:[Development of a new evaluation system for visual function]. 1565 88

Five mouse models with known alterations of resistance to oxidative damage were compared by slit lamp examination for the presence and degree of advancement of age-related cataract in young adult and old animals along with wild type controls. A group of young and old normal C57BL/6Jax mice were examined first to constitute a standard, and they were found to exhibit age-related cataract development. Following this, four models on the C57BL/6 background with imposed genetic alterations affecting anti-oxidant enzyme presence or activity, and one outbred model in which a deletion blocked the growth hormone/IGF-1 axis, were similarly examined. There was no evidence of foetal or juvenile cataract development in any of these models, and an age-related severity for lens opacities was shown between young adult and old mice in all groups. Model 1, mice null for the anti-oxidant gene glutathione peroxidase-1 (GPX1) had significantly advanced cataracts in older mice vs. same age controls. In mouse model 2 hemizygous knockout of SOD2 (MnSOD) did not affect age-related cataract development. In model 3 combining the GPX1 and SOD2 deficiencies in the same animal did not advance cataract development beyond that of the GPX1 null alone. In model 4 the addition of anti-oxidant protection in the lens by transfection of human catalase targeted only to the mitochondria resulted in a significant delay in cataract development. The 5th model, growth hormone receptor knockout (GHR-/-) mice, also demonstrated a significant reduction in age-related cataract development, as well as dwarfism. These findings, in general, support the oxidative theory of age-related cataract development. The exception, the partial deletion of SOD2 in the hemizygous KO model, probably did not represent a sufficiently severe deprivation of anti-oxidant protection to produce pathologic changes in the lens.
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PMID:Age-related cataract progression in five mouse models for anti-oxidant protection or hormonal influence. 1612 95

Despite very different life expectancies, a 2-year-old mouse, a 12-year-old dog, a 32-year-old chimpanzee or an 80-year-old man will share many common deficits such as a reduction in tissue elasticity, immunological responses, muscular strength, sensory perceptions, reflexes, as well as memory losses and increase of age-associated diseases (osteoporosis, osteoarthritis, type II diabetes, cardiovascular diseases, cataract and macular degeneration, neurodegenerative diseases, to name only a few...). With the increase of life expectancy in human species, ageing has become a major concern for the society, both at the human and financial level. The main challenge for biologists studying ageing is to understand how the multiple effects quoted above, so easily identifiable in various species, are nonetheless so coordinate among individuals of a given species. The acquisition of this fundamental knowledge will be essential to reach the ultimate goal of healthy ageing for human populations. At the present time, three types of recent developments on ageing research can be distinguished: 1) A consensus on evolutionist theory of ageing is developing. This theory is based on the fact that long-lived species usually arise from protected ecological niches. It implies that phenotypes which are expressed late in "aged survivors" are beyond natural selection. So, alleles underlying this late expression being adaptive or not ("good" or "bad"), contribute only slightly to the pool of genes of the following generation. 2) Study of laboratory models like the nematode C. elegans or fly D. melanogaster have enabled the observation that single-gene invalidation can increase lifespan. Interestingly, some of these changes seem to imply a common process through insulin/IGF-1 (insulin like growth factor-I) orthologue, energy metabolism and growth implicated hormones, as well as protection against free radicals. 3) In the mouse, several genes mutation increase lifespan and are associated with a decrease in growth hormone (GH) secretion as well as its main effector IGF-1. The study of such transgenic mutants, in parallel with the well-known effect of the caloric restriction on ageing, open several tracks which should allow determining common mechanisms which regulate the mammalian lifespan.
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PMID:[Biological aspects of longevity and ageing]. 1622 10

Lens regeneration occurs in New Zealand albino rabbits after endocapsular lens extraction, if the anterior and posterior capsules remain relatively intact. Research beginning in the 19th century showed that regeneration of the lens begins as early as 2 weeks postoperatively, depends on the size of the capsulotomy and how it has scarred, and is faster in younger animals. More recently, implantation of embryonic ectoderm at the time of lens removal has been shown to improve the growth and quality of the regenerated lenses. Lens fiber differentiation follows a process similar to embryological development with proliferation of epithelial cells along the anterior and posterior capsule, elongation of the posterior epithelial cells, and differentiation into lens fibers. Signals required for lens fiber differentiation include FGF, IGF-1, and TGF-beta. Identifying other signals, and providing these factors to the regenerating lens, could speed up lens regeneration and improve normality of the resulting structure. The regenerated lenses contain the same proteins as normal lenses, including all the major crystallins (alpha, beta, and gamma). However, regenerated lenses have typically been irregular in shape due to lack of lens growth at the site of the anterior capsulotomy and its adhesion to the posterior capsule. Sealing the capsulotomy and refilling the bag to maintain its shape seem to allow for more normal lens regeneration. Lens regeneration is a potential approach to restoring normal vision after cataract surgery. Importantly, lenses have been shown to regenerate after removal of cataracts in several mammals, and primate lenses do have regenerative capability.
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PMID:Lens regeneration in mammals: a review. 1641 61

Diabetes Mellitus (DM) is a serious medical problem that causes long-term systemic complications and considerable associated morbidity. DM can cause retinopathy (DRP), maculopathy, cataract, optic neuropathy, defects of eye muscles. DM is a risk factor for acute infectious conjunctivitis, bacterial keratitis, herpes virus infections and endophtalmitis. Elevated blood glucose induces structural, physiological and hormonal changes which affect retinal capillaries. DRP is recognized by loss of pericyte function and capillary occlusions together leading to breakdown of blood-retinal barrier, edematous changes and proliferation of vessels and fibrous tissue. Depending on stage of DRP, there are different preferable therapeutic approaches applied. In the case of ETDRS, in the area of leakage focal treatment should be performed, while panretinal photocoagulation is applied towards ischemic areas or beginning proliferations. Vitreal haemorrhage followed by fibroproliferative changes or tractional retinal detachment is treated by vitrectomy alone or in combination with ILM peeling. In pathogenesis of DRP, Insulin Growth Factor (IGF-1) can play an important role in production of VEGF (Vascular Endothelial Growth Factor). Hypoxia can up-regulate VEGF expression levels leading to pathologic ocular neovascularisation. An application of intravitreal corticosteroid treatment modulates vascular permeability by suppressing the production of VEGF, reducing both extracellular matrix metalloproteinase activity and basic fibroblast growth factor, decreasing major histocompatibility complex 2 Ag expression levels, and inhibiting activity of inflammatory cells. Clinical effects of treatment using intravitreal corticosteroids are evaluated by reduction of macular thickness and visual improvement. Intravitreal use of Anti-VEGF drugs, Pegaptanib, Ranibizumab and Bevacizumab can modify vasoproliferation, trigger macular edema, and, therefore, influence a prognosis for visual loss.
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PMID:Eye disorders in diabetes: potential drug targets. 1853 2

In 2003, we reported on 2 cases of nonproliferative and proliferative diabetic retinopathy, subsequent to HbA1c reduction by intensive insulin therapy (so-called early worsening of diabetic retinopathy). This acute condition could partly be reversed by discontinuation of intensive insulin therapy, whereby glycemia increased and serum IGF-1 concentration decreased [Ophthalmologica 2003;217:373-377]. On review 7 years later, both type-2 diabetic patients were on insulin therapy but had failed to achieve good glycemic control. One patient had mild background retinopathy on both eyes, with visual acuity of 1.0 and 0.7 after cataract extraction plus intravitreal triamcinolone injection. The 2nd patient was blind in one eye from secondary glaucoma due to vitrectomy and silicone oil filling; the fellow eye displayed residual retinal neovascularization with a hyaloid membrane and a visual acuity of 0.5. Hence, early worsening as opposed to late worsening of diabetic retinopathy seems to benefit from therapeutic suppression of growth factor action.
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PMID:Downregulation of serum IGF-1 for treatment of early worsening of diabetic retinopathy: a long-term follow-up of two cases. 1994 May 32