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| March 2007 | Inside IOVS | Volume 48/3 |
Manganese-Enhanced Magnetic Resonance Imaging and Choroidal Melanoma
Braun et al. (p. 963) used manganese-enhanced magnetic resonance imaging (MEMRI) to image experimental human choroidal melanomas growing in the eyes of nude rats. MEMRI permitted the simultaneous evaluation of the structure and function of the tumor and the neighboring retina. The use of MEMRI in this choroidal melanoma model will permit the study of the impact of tumor growth on the neighboring retina and will allow the simultaneous evaluation of treatment-related side effects in the same eye. Although not yet evaluated, it may be possible to monitor choroidal melanoma progression and/or treatment response clinically using MEMRI in patients.
Retinoschisin: Localization and Molecular Interactions
Retinoschisin (RS), a 24 kDa secreted protein, is believed to function as an adhesive in preserving the structural and functional integrity of the retina, but little is known about the cellular and molecular basis of its function. Mutations in RS cause X-linked retinoschisis (XLRS), a disease commonly associated with splitting of the inner retinal layers. The study by Vijayasarathy et al. (p. 991) reveals that RS densely localizes on the photoreceptor inner segment plasma membrane where it is associated primarily with the outer leaflet through anionic phospholipids and divalent cations. These findings raise the possibility that RS regulates photoreceptor stability and architecture as well as inner retinal structure.
Age-Related Macular Degeneration in a Rural Population in North India
In high income countries age-related macular degeneration (AMD) is the main cause of adult blindness. There is little information on this condition in developing countries, especially in countries such as India that are experiencing a rapid growth in the older population. Gupta et al (p. 1007) report the results of a population-based survey of people aged 50 years and older in a rural locale in north India, using digitized fundus images independently graded at a single center. Soft drusen were found in approximately one-third of participants and pigmentary irregularities in 10%. AMD was present in 1.4%. These results suggest that AMD prevalence may be similar to that observed in western settings.
NGF Gene Therapy in Corneal Transplantation
Nerve growth factor (NGF), a member of the neurotrophin family, is a trophic molecule originally identified and characterized by its functions in the nervous system. Gong et al. (p. 1043) demonstrate how NGF expression modulates corneal allograft rejection. The authors show that local over-expression of NGF significantly prolongs the survival of corneal allografts. Moreover, co-application of systemic immunosuppression further improved graft survival, as well as the protective effects and graft endothelial integrity provided by local NGF gene therapy. A combined gene therapy/conventional therapy approach could be a useful strategy to prevent corneal allograft rejection.
A Variant in the Gene LOC387715 and Age-Related Macular Degeneration
Ross et al. (p. 1128) confirmed that people carrying a common variant in the gene LOC387715 are at higher risk of developing age-related macular degeneration by using two case-control sets taken from well-established epidemiological studies on the disease. They also found that the LOC387715 variant leads to a much higher risk for advanced AMD than for early or intermediate stages. The variant does not cause a significant difference in risk between the advanced AMD subtypes, "wet" (neovascular) and "dry" (geographic atrophy). While a previous study showed that this LOC387715 variant interacts with smoking to give smokers a much higher risk of AMD, the present results do not find strong evidence for this interaction.
Functional Deficits in Amblyopia
Amblyopia is the commonest form of unilateral and binocular visual impairment among children and younger adults. Its treatment is time-consuming and costly, prompting calls to justify current practice. Grant et al. (p. 1139) show that simple reach-to-grasp movements are defective in adult amblyopes, with deficits in visual control of the hand increasing with increasing spatial- and stereo-acuity losses. These findings add to growing evidence of functional disability in amblyopia. While supporting the validity of treatment, they further suggest that clinicians place greater emphasis on interventions (e.g., refractive adaptation) that promote binocularity and give more explicit consideration to visuomotor performance when evaluating their outcomes.
Advanced Glycation End Products and Glaucoma
Tezel et al. (p. 1201) used immunohistochemical analysis to reveal enhanced accumulation of advanced glycation end products (AGEs) in the glaucomatous human retina and optic nerve head. Since AGE generation is an age-dependent process associated with oxidative stress, these findings suggest that an accelerated aging process accompanies neurodegeneration in glaucomatous eyes. One of the consequences of AGE accumulation in glaucomatous eyes may be the contribution of these aggregates to increased rigidity of the lamina cribrosa in the glaucomatous optic nerve head. The presence of the specific receptor, RAGE, on RGCs and glia also makes them susceptible to AGE-mediated events through receptor-mediated signaling, which may promote cell death and/or dysfunction.
RAGE and RPE Secretion of VEGF
Ma et al. (p. 1355) demonstrate that activation of receptor for advanced glycation end products (RAGE) by its ligands, including advanced glycation end products, amyloid-b peptide, and S100B/calgranulins, some of which are known to be present in drusen and increased in aging Bruch's membrane, can directly induce ARPE-19 cells to increase secretion of VEGF. The results suggest that one "upstream" pathway for RPE cells to upregulate VEGF production in the aging macula is the RAGE axis and that this pathway may be an important therapeutic target for prophylaxis against neovascular macular disease.
Estrogen Receptor Variations and Risk of Age-Related Macular Degeneration
It has been suggested that estrogen deficiency might be involved in the pathogenesis of age-related macular degeneration (AMD). Boekhoorn et al. (p. 1012) investigated whether genetic variations of the estrogen receptor a gene, which are associated with serum estrogen levels, are a risk factor for AMD. They showed an increased risk of late, and especially wet, AMD in persons with one or two copies of ESR1 PvuII-XbaI haplotype 1. These findings support a pathophysiological role of estrogen in the development of AMD.
Laser-Generated Second Harmonic Signals and Corneal Fine Structure
Morishige et al. (p. 1087) used a femtosecond laser to generate second harmonic signals (SHG) from collagen to explore the 3-dimensional stromal collagen organization. With SHG, normal corneas were found to contain a prominent population of interwoven, 'sutural' lamellae that insert into Bowman's layer and run transversely to a depth of 120 mm in the anterior cornea. 'Sutural' lamellae are absent, greatly reduced, or abnormal in keratoconus corneas, suggesting that these structures may play a role in the pathogenesis of this disorder. Identifying the relationship between 'sutural' lamellae and corneal biomechanics may be important to better understanding keratoconus, ectasia, and other refractive abnormalities.
Erythropoietin: A Potential Adjunct Therapy for Glaucoma Patients
Zhong et al. (p. 1212) suggest that systemic treatment with erythropoietin (EPO) can effectively prevent retinal ganglion cell (RGC) loss in a murine model of glaucoma, independent of intraocular pressure (IOP). IOP-lowering drugs are the only treatment currently used for glaucoma – even for glaucoma involving normal IOP – but these drugs only provide partial RGC protection. EPO used as an adjunct therapy may therefore reduce vision loss with glaucoma. Further investigations into EPO efficacy and mechanisms in RGC neuroprotection are warranted.
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