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| August 2006 | Inside IOVS | Volume 47/8 |
Construction of Synthetic Corneas by Tissue Engineering
Tissue engineering is an emerging field that aims to regenerate natural tissues and create new tissues using cells and biomaterials. By using tissue engineering, Alaminos et al. (p. 3311) have been able to generate a living artificial cornea in the laboratory. For that purpose, the authors use rabbit cornea cells and an acellular scaffold of human fibrin and agarose. This technology could permit in the near future the construction of synthetic human corneas for transplant. These organs would overcome the present disadvantages of heterologous corneal transplantation.
Sustained Rapamycin Delivery for Prevention of Corneal Graft Rejection
Rapamycin has been widely used to inhibit immune rejection after solid organ transplantation. However, to date, it can only be administered systemically. As described in this study, Shi et al. (p. 3339) developed a biodegradable rapamycin drug delivery system and implanted it into the anterior chamber of a rabbit model for prevention of high-risk corneal allograft rejection and neovascularization. It appears that the rapamycin drug delivery system can significantly prolong high-risk allograft survival and inhibit corneal neovascularization.
EP3 Receptor and IOP Reduction by Prostaglandin Analogues
While the FP receptor is an example of intraocular pressure (IOP) control via prostanoid receptors, it is unknown whether the other prostanoid receptors have a role in the control of IOP. Ota et al. (p. 3395) investigated the role of EP1, 2, and 3 receptors using receptor knockout mice. Deletion of each receptor showed no effect on the physiological IOP. However, IOP reduction by prostaglandin analogues was attenuated in EP3 knockout mice. Also, pretreatment by nonsteroidal anti-inflammatory medications attenuated prostaglandin analogue-induced IOP reduction in wild-type but not in EP3 knockout mice. The EP3 receptor may have an additive role in the reduction of IOP via endogenously produced prostaglandins.
Gene Therapy for Choroidal Neovascularization with Short Hairpin RNAs
Choroidal neovascularization is the leading cause of blindness in age-related macular degeneration (AMD). Several clinical trials targeting vascular endothelial growth factor (VEGF) are currently under way, but those treatments require repeat intraocular administration and are hence associated with significant side effects including endophthalmitis, retinal detachment, and cataract. Cashman et al. (p. 3496) demonstrate use of adenovirus vectors expressing short hairpin RNAs to silence VEGF in a mouse model of wet AMD with a single intraocular injection. The approach reported in this study may lead to the development of long-term therapies for the wet form of AMD.
(Hydroxy-) Chloroquine Retinopathy Re-examined
The appropriate screening for chloroquine/hydroxychloroquine retinopathy has been under debate for a long time. Kellner et al. (p. 3531) examined two recently developed methods, multifocal electroretinography and fundus autofluorescence, which appear to be very sensitive tools to detect early changes of retinal function and retinal pigment epithelial morphology. These techniques optimize screening abilities for earlier detection of toxic side effects in chloroquine/hydroxychloroquine treatment. In addition, application of these tools in other studies for evaluation of retinal toxicity or early detection of other retinal disorders appears to be feasible.
Retinal Vascular Caliber: An Inherited Trait or a Reflection of Blood Pressure?
Taarnhøj et al. (p. 3539) showed that retinal vessel calibers may be a primary genetic characteristic (heritability was 70% for artery diameters) rather than a reflection of variations in blood pressure. Recent studies have shown that general arterial narrowing precedes the development of severe hypertension, suggesting that these changes are an element in the pathogenesis. Arterioles may be effectors rather than sensors in relation to arterial hypertension. The hypothetical inference may be that the antihypertensive medications that most effectively reduce the morbidity and mortality associated with arterial hypertension are the ones that most effectively eliminate retinal arteriolar contraction, independently of their effect on blood pressure.
Mechanism of Pathogenesis in Stargardt-like Disease
As described by Raz-Prag et al. (p. 3603), detailed characterization of a heterozygous knockout mouse of Elovl4, the gene implicated in Stargardt-like disease in humans, revealed that despite a reduction in mRNA levels of Elovl4 the mice showed only minimal abnormalities. This provides the first in vivo evidence that Elovl4 haploinsufficiency is not the underlying key mechanism in this disease and implicates the dominant negative mechanism as the cause in humans with a deletion mutation. Together with complementary animal models and in vitro studies, this model provides information that may help elucidate the structure and function of the ELOVL4 protein and the disease mechanism on the cellular level.
Photoreceptor Degeneration Leads to Decreased Retinal Oxygen Consumption
Hereditary retinal degenerations in humans and animals are accompanied by a severe attenuation of the major vessels of the retinal circulation. Padnick-Silver et al. (p. 3683) measured intraretinal oxygen in anesthetized Abyssinian cats with a progressive photoreceptor degeneration. They showed that this attenuation could be explained by a progressive decrease in photoreceptor oxygen consumption, which in turn increased the flux of oxygen from the choroidal circulation to the inner retina. The retinal circulation responds to metabolic factors, and it appears that chronically elevated oxygen not only constricts this circulation, but destroys it. The decrease in oxygen consumption occurred at approximately the same rate as the loss of the a-wave of the ERG, so the a-wave is not only a measure of function, but could be used as a rough measure of photoreceptor metabolism.
Nimodipine Plasma Concentration and the Retinal Blood Flow
Michelson et al (p. 3479) measured simultaneously both retinal blood flow and plasma concentration of the calcium antagonist nimodipine during repeated dosing. They showed that oral nimodipine administered in higher doses than in previous studies significantly increases retinal perfusion in healthy subjects. In normal tension glaucoma (NTG) the retinal blood flow is known to be significantly reduced. Consideration of individual factors (i.e., the presence of a reactive vascular tone, the large variance of plasma concentrations) and adjustment of the calcium antagonist dosage by monitoring the retinal blood flow may be beneficial for NTG patients. Future studies should investigate the efficacy of a chronic adjusted treatment with calcium antagonists in glaucomatous patients.
Acuities with Macular Hole Patients Depend on the Acuity Chart
Visual acuity is the most widely used measure to evaluate functional treatment outcome after macular hole surgery. It seems, however, that the choice of acuity chart has great impact on this outcome measure. Wittich et al. (p. 3690) demonstrate that acuities on recognition and resolution charts differ by up to 5 lines before and 3 lines after surgical treatment. This clinically relevant discrepancy reaffirms that the choice of eye chart in the context of ophthalmic research and practice warrants careful attention.
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