Temporal retinal thinning might be an early diagnostic indicator in male pediatric X-linked Alport syndrome.

AIM: To evaluate temporal retinal thinning changes in retinal layers using spectral-domain optical coherence tomography (SD-OCT) in pediatric X-linked Alport syndrome (XLAS) patients. METHODS: A retrospective case-control study. SD-OCT scans of pediatric patients diagnosed with XLAS and age- and sex-matched healthy control participants were reviewed. Automated segmentation of SD-OCT scans was induced to analyze the retinal thickness (RT) of different layers. The temporal thinning index (TTI) was calculated for each layer and compared between the patients and the control group. RESULTS: Forty-three pediatric XLAS patients and 60 healthy controls were included. Temporal retinal thinning was present in 33 patients (76.74%), while 28 patients (65.11%) had severe pathological temporal retinal thinning and 5 patients (11.63%) had moderate thinning. The temporal inner sector RT (P<0.0001), the temporal outer sector RT (P<0.0001), and the nasal outer sector RT (P=0.0211) were significantly thinner in the XLAS male patients. The TTI of the total retina was significantly higher in the XLAS group than in the control group (P<0.0001). The TTI of the inner retina layers (P<0.0001), ganglion cell layer (P<0.0001), inner plexiform layer (P<0.0001), inner nuclear layer (P<0.0001), and outer nuclear layer (P<0.0001) were significantly higher in the XLAS group. The central RT of the XLAS group was significantly thinner than that of the control group (P<0.0001). CONCLUSION: Temporal retinal thinning appears early in XLAS patients, especially in male patients. The thinning is mainly caused by structural abnormalities of the inner retina. This suggests that temporal retinal thinning could be helpful for the early diagnosis and follow-up of XLAS with noninvasive SD-OCT examination.

Absence of ephrin-A2/A3 increases retinal regenerative potential for Müller cells in Rhodopsin knockout mice.

Müller cells (MC) are considered dormant retinal progenitor cells in mammals. Previous studies demonstrated ephrin-As act as negative regulators of neural progenitor cells in the retina and brain. It remains unclear whether the lack of ephrin-A2/A3 is sufficient to promote the neurogenic potential of MC. Here we investigated whether the MC is the primary retinal cell type expressing ephrin-A2/A3 and their role on the neurogenic potential of Müller cells. In this study, we showed that ephrin-A2/A3 and their receptor EphA4 were expressed in retina and especially enriched in MC. The level of ephrinAs/EphA4 expression increased as the retina matured that is correlated with the reduced proliferative and progenitor cell potential of MC. Next, we investigated the proliferation in primary MC cultures isolated from wild-type and A2-/- A3-/- mice by 5-ethynyl-2'-deoxyuridine (EdU) incorporation. We detected a significant increase of EdU+ cells in MC derived from A2-/- A3-/- mice. Next, we investigated the role of ephrin-A2/A3 in mice undergoing photoreceptor degeneration such as Rhodopsin knockout (Rho-/-) mice. To further evaluate the role of ephrin-A2/A3 in MC proliferation in vivo, EdU was injected intraperitoneally to adult wild-type, A2-/- A3-/- , Rho-/- and Rho-/- A2-/- A3-/- mice and the numbers of EdU+ cells distributed among different layers of the retina. EphrinAs/EphA4 expression was upregulated in the retina of Rho-/- mice compared to the wild-type mice. In addition, cultured MC derived from ephrin-A2-/- A3-/- mice also expressed higher levels of progenitor cell markers and exhibited higher proliferation potential than those from wild-type mice. Interestingly, we detected a significant increase of EdU+ cells in the retinas of adult ephrin-A2-/- A3-/- mice mainly in the inner nuclear layer; and these EdU+ cells were co-localized with MC marker, cellular retinaldehyde-binding protein, suggesting some proliferating cells are from MC. In Rhodopsin knockout mice (Rho-/- A2-/- A3-/- mice), a significantly greater amount of EdU+ cells were located in the ciliary body, retina and RPE than that of Rho-/- mice. Comparing between 6 and 12 weeks old Rho-/- A2-/- A3-/- mice, we recorded more EdU+ cells in the outer nuclear layer in the 12-week-old mice undergoing severe retinal degeneration. Taken together, Ephrin-A2/A3 are negative regulators of the proliferative and neurogenic potentials of MC. Absence of ephrin-A2/A3 promotes the migration of proliferating cells into the outer nuclear layer and may lead to retinal cell regeneration. All experimental procedures were approved by the Animal Care and Use Committee at Schepens Eye Research Institute, USA (approval No. S-353-0715) on October 24, 2012.

Intrinsic determinants of optic nerve regeneration.

OBJECTIVE: To review the functions of these intracellular signals in their regulation of retinal ganglion cell (RGC) axon regeneration. DATA SOURCES: Relevant articles published in English or Chinese from 1970 to present were selected from PubMed. Searches were made using the terms "intrinsic determinants, axon regeneration, RGC, optic nerve regeneration, and central nervous system axon regeneration." STUDY SELECTION: Articles studying the mechanisms controlling RGC and central nervous system (CNS) axon regeneration were reviewed. Articles focusing on the intrinsic determinants of axon regeneration were selected. RESULTS: Like other CNS neurons of mammals, RGCs undergo a developmental loss in their ability to grow axons as they mature, which is a critical contributing factor to the failure of nerve regeneration and repair after injury. This growth failure can be attributed, at least in part, by the induction of molecular programs preventing cellular overgrowth and termination of axonal growth upon maturation. Key intracellular signals and transcription factors, including B cell lymphoma/leukemia 2, cyclic adenine monophosphate, mammalian target of rapamycin, and Krüppel-like transcription factors, have been identified to play central roles in this process. CONCLUSIONS: Intense effort and substantial progress have been made to identify the various intrinsic growth pathways that regulate RGC axon regeneration. More work is needed to elucidate the mechanisms of and the interrelationship between the actions of these factors and to successfully achieve regeneration and repair of the severed RGC axons.

[The research advances of intrinsically photosensitive retinal ganglion cells].

Intrinsically photosensitive retinal ganglion cells (ipRGC) are photosensitive cell besides rods and cones. These cells are crucial for circadian photoentrainment and pupillary light reflex. Some chronobiologists and ophthalmologists have focused on these ipRGC in recent years. However, little research has been done by Chinese scientists. Here we review the recent advances about biological features, physical functions and clinical applications of ipRGC.