Dataset Information

Aged peripheral retinal lesions originating from the ciliary body sweep away the retinal pigmented epithelium.

ABSTRACT: AIMS: To investigate age-related lesions in the far-anterior retina that migrate from the ciliary body (CB) and how they affect the neural retina and retinal pigmented epithelium (RPE). METHODS: One eye from three healthy subjects aged 87, 92 and 93 years were used. Retinae were photographed, embedded in resin and then sectioned at 2 ?m. RESULTS: Multiple elliptically shaped lesions were present in the CB. Larger lesions extended into the peripheral retina. Lesions resulted from deposits that had lenticular qualities. These develop centrally along Bruch's membrane sweeping away the RPE, such that piles of RPE cells were present around the deposits that resulted in retinal atrophy. The internal composition of the deposits revealed large numbers of spherical bodies, unlike those seen in drusen. RPE cells adjacent to these deposits and their underlying lesions became highly irregular, with melanin granules spacing themselves out within the cell and adopting similar orientations. This is a highly distinctive feature. CONCLUSIONS: These far-anterior deposits were different in nature from drusen in terms of morphology, composition and origin. They swept away the RPE, exposing the Bruch's membrane and isolating the retina, leading to atrophy. They appeared to originate from the CB and progressed centrally. The deposits may have developed from the ciliary muscle, which would account for their elongated orientation. Their impact on melanin distribution in RPE cells was unexpected and unusual, implying that they release a signal that influences melanin organisation.

SUBMITTER: Begum R

PROVIDER: S-EPMC3355342 | biostudies-other | 2012 Jun

REPOSITORIES: biostudies-other

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Aged peripheral retinal lesions originating from the ciliary body sweep away the retinal pigmented epithelium.

Begum Rana R Jeffery Glen G

The British journal of ophthalmology 20120318 6

<h4>Aims</h4>To investigate age-related lesions in the far-anterior retina that migrate from the ciliary body (CB) and how they affect the neural retina and retinal pigmented epithelium (RPE).<h4>Methods</h4>One eye from three healthy subjects aged 87, 92 and 93 years were used. Retinae were photographed, embedded in resin and then sectioned at 2 μm.<h4>Results</h4>Multiple elliptically shaped lesions were present in the CB. Larger lesions extended into the peripheral retina. Lesions resulted fr ...[more]

PMID: 22426947

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Project description:One of the promises in regenerative medicine is to regenerate or replace damaged tissues. The embryonic chick can regenerate its retina by transdifferentiation of the retinal pigmented epithelium (RPE) and by activation of stem/progenitor cells present in the ciliary margin. These two ways of regeneration occur concomitantly when an external source of fibroblast growth factor 2 (FGF2) is present after injury (retinectomy). During the process of transdifferentiation, the RPE loses its pigmentation and is reprogrammed to become neuroepithelium, which differentiates to reconstitute the different cell types of the neural retina. Somatic mammalian cells can be reprogrammed to become induced pluripotent stem cells by ectopic expression of pluripotency-inducing factors such as Oct4, Sox2, Klf4, c-Myc and in some cases Nanog and Lin-28. However, there is limited information concerning the expression of these factors during natural regenerative processes. Organisms that are able to regenerate their organs could share similar mechanisms and factors with the reprogramming process of somatic cells. Herein, we investigate the expression of pluripotency-inducing factors in the RPE after retinectomy (injury) and during transdifferentiation in the presence of FGF2.We present evidence that upon injury, the quiescent (p27(Kip1)+/BrdU-) RPE cells transiently dedifferentiate and express sox2, c-myc and klf4 along with eye field transcriptional factors and display a differential up-regulation of alternative splice variants of pax6. However, this transient process of dedifferentiation is not sustained unless FGF2 is present. We have identified lin-28 as a downstream target of FGF2 during the process of retina regeneration. Moreover, we show that overexpression of lin-28 after retinectomy was sufficient to induce transdifferentiation of the RPE in the absence of FGF2.These findings delineate in detail the molecular changes that take place in the RPE during the process of transdifferentiation in the embryonic chick, and specifically identify Lin-28 as an important factor in this process. We propose a novel model in which injury signals initiate RPE dedifferentiation, while FGF2 up-regulates Lin-28, allowing for RPE transdifferentiation to proceed.

Project description:GABA is more than the main inhibitory neurotransmitter found in the adult CNS. Several studies have shown that GABA regulates the proliferation of progenitor and stem cells. This work examined the effects of the GABA(A) receptor system on the proliferation of retinal progenitors and non-pigmented ciliary epithelial (NPE) cells. qRT-PCR and whole-cell patch-clamp electrophysiology were used to characterize the GABA(A) receptor system. To quantify the effects on proliferation by GABA(A) receptor agonists and antagonists, incorporation of thymidine analogues was used. The results showed that the NPE cells express functional extrasynaptic GABA(A) receptors with tonic properties and that low concentration of GABA is required for a baseline level of proliferation. Antagonists of the GABA(A) receptors decreased the proliferation of dissociated E12 NPE cells. Bicuculline also had effects on progenitor cell proliferation in intact E8 and E12 developing retina. The NPE cells had low levels of the Cl-transporter KCC2 compared to the mature retina, suggesting a depolarising role for the GABA(A) receptors. Treatment with KCl, which is known to depolarise membranes, prevented some of the decreased proliferation caused by inhibition of the GABA(A) receptors. This supported the depolarising role for the GABA(A) receptors. Inhibition of L-type voltage-gated Ca(2+) channels (VGCCs) reduced the proliferation in the same way as inhibition of the GABA(A) receptors. Inhibition of the channels increased the expression of the cyclin-dependent kinase inhibitor p27(KIP1), along with the reduced proliferation. These results are consistent with that when the membrane potential indirectly regulates cell proliferation with hyperpolarisation of the membrane potential resulting in decreased cell division. The increased expression of p27(KIP1) after inhibition of either the GABA(A) receptors or the L-type VGCCs suggests a link between the GABA(A) receptors, membrane potential, and intracellular Ca(2+) in regulating the cell cycle.

Dataset Information

Aged peripheral retinal lesions originating from the ciliary body sweep away the retinal pigmented epithelium.

Publications

Aged peripheral retinal lesions originating from the ciliary body sweep away the retinal pigmented epithelium.

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