Diode laser TSCP aided in the control of IOP and maintenance of vision but did not eliminate the need for topical glaucoma medication during the period of clinical follow-up.
The purpose of this study was to evaluate whether immune responses interfered with gene therapy rescue using subretinally delivered recombinant adeno-associated viral vector serotype 2 carrying the RPE65 cDNA gene driven by the human RPE65 promoter (rAAV2.hRPE65p.hRPE65) in the second eye of RPE65À/À dogs that had previously been treated in a similar manner in the other eye. Bilateral subretinal injection was performed in nine dogs with the second eye treated 85-180 days after the first. Electroretinography (ERG) and vision testing showed rescue in 16 of 18 treated eyes, with no significant difference between first and second treated eyes. A serum neutralizing antibody (NAb) response to rAAV2 was detected in all treated animals, but this did not prevent or reduce the effectiveness of rescue in the second treated eye. We conclude that successful rescue using subretinal rAAV2.hRPE65p.hRPE65 gene therapy in the second eye is not precluded by prior gene therapy in the contralateral eye of the RPE65À/À dog. This finding has important implications for the treatment of human LCA type II patients. Gene Therapy (2011) The condition is characterized by severe visual impairment in dim light, typically progressing to complete blindness in the second decade of life. LCA type II results from mutations in the RPE65 gene, and accounts for 10-15% of LCA cases. 2,3 RPE65 encodes a protein that forms an essential component of the visual cycle and is expressed within the retinal pigment epithelium. 3 The visual cycle is responsible for the supply of the chromophore, 11-cis-retinal, to the photoreceptor cells for combination with the rod and cone opsins to form the visual pigments. RPE65 is an isomerohydrolase that converts esters of vitamin A to 11-cis-retinol for subsequent oxidation to 11-cis-retinal prior to transport to the photoreceptors. A spontaneous 4 basepair deletion in RPE65 in the Briard breed of dog results in a premature stop codon and an absence of RPE65 gene product, resulting in a very similar phenotype to LCA type II. 4 Affected dogs have markedly reduced vision and an abnormal electroretinogram with greatly elevated threshold of responses. 4,5 The similarities between the human and canine disease resulting from RPE65 mutations, make the RPE65À/À Briard a valuable large animal model for LCA type II.Dramatic restoration of vision with gene therapy was first reported in the canine RPE65À/À model of LCA. 6 A number of studies have shown rod and cone photoreceptor rescue using rAAV vectors to deliver a normal copy of the RPE65 gene via a subretinal injection in the RPE65 mutant Briard. [6][7][8][9][10][11][12][13] On the basis of the great success of the canine trials, phase I/II clinical trials of rAAV-RPE65 gene replacement therapy in human LCA patients have started with the first reported results showing great promise. 14-16 Thus far in all human patients only one eye has been treated. A critical aspect of the management of LCA
Recent clinical trials of retinal pigment epithelium gene (RPE65) supplementation therapy in Leber congenital amaurosis type 2 patients have demonstrated improvements in rod and cone function, but it may be some years before the effects of therapy on photoreceptor survival become apparent. The Rpe65-deficient dog is a very useful pre-clinical model in which to test efficacy of therapies, because the dog has a retina with a high degree of similarity to that of humans. In this study, we evaluated the effect of RPE65 gene therapy on photoreceptor survival in order to predict the potential benefit and limitations of therapy in patients. We examined the retinas of Rpe65-deficient dogs after RPE65 gene therapy to evaluate the preservation of rods and cone photoreceptor subtypes. We found that gene therapy preserves both rods and cones. While the moderate loss of rods in the Rpe65-deficient dog retina is slowed by gene therapy, S-cones are lost extensively and gene therapy can prevent that loss, although only within the treated area. Although LM-cones are not lost extensively, cone opsin mislocalization indicates that they are stressed, and this can be partially reversed by gene therapy. Our results suggest that gene therapy may be able to slow cone degeneration in patients if intervention is sufficiently early and also that it is probably important to treat the macula in order to preserve central function.
Summary In the neonatal foal septic arthritis is an important cause of morbidity that may limit future athletic performance. This is often despite a good prognosis for resolution of joint infection. This article presents a review of the diagnosis and treatment of septic arthritis in foals less than 2 months of age, including an overview of our current understanding of inflammatory joint disease in the neonate. Management options are described, with emphasis on tailoring therapy to the individual foal based on accurate staging and monitoring of the disease process. Special considerations relevant to the immature animal are addressed.
Sinonasal cyst should be a differential diagnosis for retrobulbar disease in horses. Exophthalmia may be the only clinical finding in horses with a sinonasal cyst.
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