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| December 2002 | Inside IOVS | Volume 43/12 |
| Genes, Gene Therapy, and Ocular Function |
p130 Expression in Retinoblastoma
The retinoblastoma gene (RB/p105) is well known to be responsible for the pathogenesis of human retinoblastomas. Bellan et al. (p. 3602) studied the expression of a different tumor suppressor gene belonging to the retinoblastoma family (pRb2/p130) and found that its expression was altered in a certain number of cases with a lower apoptotic index and lower degree of differentiation. As the study included a considerable number of tumors with a low grade of differentiation and a very restricted expression of p130, this tumor suppressor gene may also be involved in the pathogenesis and progression of human retinoblastomas.
A Candidate Gene for Duane Syndrome
Duane retraction syndrome is a common cause of congenital strabism and some cases have genetic origins. As reported by Pizzuti et al. (p. 3609), two loci for autosomal dominant Duane syndrome have so far been identified on chromosomes 2q31 and 8q13. The analysis of a patient with isolated Duane syndrome and a reciprocal balanced translocation showed that a break in the chromosome 8q Duane region disrupted a gene identified as a carboxypeptidase family member, which is almost exclusively expressed in the brain. CPAH is the first candidate gene related to the Duane phenotype.
FOXC1 in Anterior Segment Dysgenesis
Mutations in the Forkhead/winged helix transcription factor gene FOXC1 are responsible for the pathogenesis of anterior segment dysgenesis, in particular, Axenfeld-Rieger anomaly. Though three different mutations have been reported earlier in FOXC1 gene, Panicker et al. (p. 3613) have described for the first time a mutation in the wing-2 region of FOXC1 protein, in a two-generation affected family. This is the region which binds to the minor groove of DNA for the mediation and regulation of transactivation by this factor. This is also a first report on FOXC1 from the Indian ethnic background.
Heredity, Environment, and Myopia
Untangling the associations between hereditary and environmental contributions to the risk of myopia has long been a goal of myopia research. Mutti et al. (p. 3633) show that parental myopia, school achievement, and near work are all associated with children’s myopia, but that parents make the more substantial contribution. Contrary to some earlier hypotheses, children do not seem to inherit a susceptibility to the myopic effects of reading and other near work, nor do they inherit the tendency to do more reading from their parents. Myopia appears to be primarily hereditary.
FIV Vectors Go with the Flow
Gene therapy has potential to provide a long-term solution to the chronic aqueous outflow abnormalities of glaucoma, but making it work will require efficient, stable and non-toxic genetic modification of the differentiated, nondividing cells of the trabecular meshwork. Feline immunodeficiency virus (FIV) vectors have been shown to effectively transduce trabecular meshwork cells of human eyes in organ perfusion culture, and TM fine structure and cellularity are preserved. Loewen et al. (p. 3686) now go on to address meshwork physiology, showing that FIV vector transduction and expression of marker genes results in only small and transient changes in outflow facility.
Gene Expression Changes in TM Cells by Dexamethasone
cDNA microarray brings gene expression analysis to a genomic scale by permitting investigators to simultaneously examine changes in the expression of thousands of genes. To elucidate further the steroid response in outflow pathway cells, Ishibashi et al. (p. 3691) evaluated gene expression profile changes induced by dexamethasone in cultured human trabecular meshwork (TM) cells using cDNA microarray. A total of 30 genes, which are differentially up-regulated in dexamethasone-treated TM cells, were identified, and the most up-regulated gene was MYOC. Changes in these genes subsequent to the dexamethasone treatment may reduce outflow facility, providing new insights into the pathogenesis of steroid-induced glaucoma.
Global Gene Expression in the TM
While the trabecular meshwork (TM) has been implicated in glaucoma, characterization of all the genes expressed by the TM is still in its infancy. Wirtz et al. (p. 3698) assess over 1000 genes expressed by human TM cell cultures. The majority of these genes are abundantly expressed by the TM and have been documented by other methods in earlier papers. Some of the TM genes are novel sequences never reported before. Characterization of these new genes will begin to enlarge the knowledge base of the TM and what potentially may go wrong in glaucoma.
BDNF Transfected IPE Enhances Survival
Kano et al. (p. 3744) transfected the BDNF gene into iris pigment epithelial cells of rats to examine BDNF’s ability to protect retinal cells in in vitro and in vivo experiments. They found a significant increase in protection against NMDA toxicity in neuroretinal cells cultured with BDNF-transfected IPE cells than with non-transfected IPE cells. The photoreceptor cells were also significantly protected against phototoxicity by subretinal transplantation of BDNF-transfected IPE cells than with non-transfected IPE cells. Transplantation of autologous IPE cells transfected with BDNF and other genes may be a useful tool for delivering genes to the retina.
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