ABSTRACT
In retinitis pigmentosa (RP), a majority of causative mutations affect genes solely expressed in rods; however, cone degeneration inevitably follows rod cell loss. Following transplantation and in vitro studies, we demonstrated the role of photoreceptor cell paracrine interactions and identified a Rod-derived Cone Viability Factor (RdCVF), which increases cone survival. In order to establish the clinical relevance of such mechanism, we assessed the functional benefit afforded by the injection of this factor in a frequent type of rhodopsin mutation, the P23H rat. In this model of autosomal dominant RP, RdCVF expression decreases in parallel with primary rod degeneration, which is followed by cone loss. RdCVF protein injections induced an increase in cone cell number and, more important, a further increase in the corresponding electroretinogram (ERG). These results indicate that RdCVF can not only rescue cones but also preserve significantly their function. Interestingly, the higher amplitude of the functional versus the survival effect of RdCVF on cones indicates that RdCVF is acting more directly on cone function. The demonstration at the functional level of the therapeutic potential of RdCVF in the most frequent of dominant RP mutations paves the way toward the use of RdCVF for preserving central vision in many RP patients.
Subject(s)
Retinal Cone Photoreceptor Cells/cytology , Retinitis Pigmentosa/metabolism , Retinitis Pigmentosa/pathology , Amino Acid Sequence , Animals , Base Sequence , Cell Death/genetics , Cell Death/physiology , Electroretinography , Gene Expression Regulation , Humans , Mice , Molecular Sequence Data , Rats , Rats, Sprague-Dawley , Rats, Transgenic , Retina/drug effects , Retina/metabolism , Retina/pathology , Retinal Cone Photoreceptor Cells/drug effects , Retinal Cone Photoreceptor Cells/metabolism , Retinitis Pigmentosa/drug therapy , Reverse Transcriptase Polymerase Chain Reaction , Sequence Alignment , Thioredoxins/chemistry , Thioredoxins/genetics , Thioredoxins/metabolism , Thioredoxins/pharmacology , Thioredoxins/physiologyABSTRACT
BACKGROUND: To evaluate the role of indocyanine green (infracyanine) in macular hole surgery. METHODS: A retrospective review of 38 consecutive eyes with macular hole, operated on with internal limiting membrane peeling (ILM), using or not using infracyanine (ICG), diluted in glucose 5% and filtered. Anatomical and functional results were analysed in each group, using visual field testing, fluorescein fundus angiography and particularly blue filter fundus photographs for the detection of retinal pigment epithelial changes and lesions of optic nerve fibres layer. RESULTS: Fifteen eyes underwent surgery without ICG and 23 eyes with ICG. The mean period of follow-up was 10 months. The duration of surgery was significantly lower in the group with ICG than without (P < 0.001). Overall, 84% of the holes closed without difference between both groups. The improvement in vision at 1, 6 and 12 months was similar in both groups. Fewer defects in the optic nerve fibres layer were observed in the group with ICG than without (P = 0.02). Staining with ICG revealed the presence of an associated epiretinal membrane in 61% of eyes, whereas it was clinically visible in only 17.5% before surgery. CONCLUSION: Using ICG for ILM peeling produced similar visual results to those obtained without ICG. It reduced significantly the duration of surgery and the trauma to the optic nerve fibres layer, without increasing the risk of retinal pigment epithelial damage. However, in the light of recent reports about the possible toxicity of ICG, its use should be restricted in clinical practice to difficult cases.
