High-Resolution Imaging of Patients with Bietti Crystalline Dystrophy with CYP4V2 Mutation.

The purpose of this study was to determine the retinal morphology of eyes with Bietti crystalline dystrophy (BCD) associated with a CYP4V2 mutation using high-resolution imaging techniques. Three subjects with BCD underwent detailed ophthalmic examinations. High-resolution fundus images were obtained with an adaptive optics (AO) fundus camera. A common homozygous mutation was detected in the three patients. Funduscopic examination of the three patients revealed the presence of crystalline deposits in the retina, and all of the crystalline deposits were also detected in the infrared (IR) images. The crystals observed in the IR images were seen as bright reflective plaques located on the RPE layer in the SD-OCT images. The clusters of hyperreflective signals in the AO images corresponded to the crystals in the IR images. High-magnification AO images revealed that the clusters of hyperreflective signals consisted of circular spots that are similar to the signals of cone photoreceptors. Most of these circular spots were detected in healthy areas in the FAF images. There is a possibility that circular spots observed by AO are residual cone photoreceptors located over the crystals.

Expression of Sox4 and Sox11 is regulated by multiple mechanisms during retinal development.

Sox11 and Sox4 play critical roles in retinal development, during which they display specific and unique expression patterns. The expression of Sox11 and Sox4 is temporally sequential, albeit spatially overlapping in some retinal subtypes. Gain-of-function and loss-of-function analyses suggested that Notch signaling suppresses Sox4 expression in the early developing retina but not during the later period of development. The levels of histone H3-acetylation and H3-lysine 4 tri-methylation at the Sox11 locus declined during development, as did the levels of Sox11. A similar but less marked change was seen for Sox4. For both genes, histone H3-lysine 27 methylation was low during development and increased markedly in the adult.

The early retinal progenitor-expressed gene Sox11 regulates the timing of the differentiation of retinal cells.

Sry-related HMG box (Sox) proteins, Sox11 and Sox4 are members of the SoxC subtype. We found that Sox11 was strongly expressed in early retinal progenitor cells and that Sox4 expression began around birth, when expression of Sox11 subsided. To analyze the roles of Sox11 and Sox4 in retinal development, we perturbed their expression patterns in retinal explant cultures. Overexpression of Sox11 and Sox4 in retinal progenitors resulted in similar phenotypes: an increased number of cone cells and dramatically decreased numbers of rod cells and Müller glia. Birth-date analysis showed that cone cells were produced at a later developmental stage than that in which cone genesis normally occurs. Sox11-knockout retinas showed delayed onset and progress of differentiation of subsets of retinal cells during the embryonic period. After birth, retinal differentiation took place relatively normally, probably because of the redundant activity of Sox4, which starts to be expressed around birth. Overexpression and loss-of-function analysis failed to provide any evidence that Sox11 and Sox4 directly regulate the transcription of genes crucial to the differentiation of subsets of retinal cells. However, histone H3 acetylation of some early proneural genes was reduced in knockout retina. Thus, Sox11 may create an epigenetic state that helps to establish the competency to differentiate. Taking our findings together, we propose that the sequential expression of Sox11 and Sox4 during retinogenesis leads to the fine adjustment of retinal differentiation by helping to establish the competency of retinal progenitors.

[Effects of vitrectomy as a treatment for proliferative diabetic retinopathy in young patients].

PURPOSE: To investigate the effects of vitrectomy as a treatment for the proliferative diabetic retinopathy (PDR) in patients under 40 years old. METHODS: Sixty eyes of 37 patients under 40 years old with PDR who had undergone vitrectomy for the first time in Juntendo University Urayasu Hospital were included in this study. Preoperative condition, operation methods, visual acuity after operation and complications both during or after operation, especially neovascular glaucoma (NVG), were reviewed retrospectively. RESULTS: Visual acuity improved in 43 eyes (72%) by more than 0.2 logMAR compared to that before the operation, remained stable in 4 eyes (6%) and deteriorated in 13 eyes (22%) by more than 0.2 logMAR compared to that before operation. Optic atrophy and phthisis caused by NVG constituted 69% of the causes of complicated final visual acuity. Male patients and patients who had both hypertension and proteinuria had significantly higher prevalence of NVG after vitrectomy (p < 0.05), and patients who retained their lens after the first vitrectomy had a significantly lower prevalence of NVG after the operation (p < 0.05). CONCLUSIONS: In young PDR patients under 40 years old, postoperative NVG was the main reason for severe visual impairment. Multifactorial causes, both general and ophthalmic seem to be implicated in the onset and progression of NVG derived from PDR.