Research progress on correlation between microRNA and retinal development / 中华实验眼科杂志

MicroRNAs (miRNAs) are small,stable RNA molecules that post-transcriptionally regulate gene expression in plants and animals by base pairing to partially complementary sequences on target mRNAs to inhibit protein synthesis.More than 200 miRNAs are reportedly expressed in the retina,and miRNA gene regulation has been shown to affect retinal development and is related to the development of both neural retina and retinal pigment epithelium,their gene-regulating function is also closely tied with the differentiation and the survival of both photoreceptor and retinal ganglion cells.Furthermore,miRNA gene regulation is also associated with retinal regeneration after injury.MiRNA controls the development of retina mainly by direct regulating the expression of some related target gene or by adjusting the components of certain signaling pathways.During the development of retina,the normal function of miRNA ensures the correct structure formation of retina,which also provides a substance basis for its normal physiological function.Herein we reviewed the recent research progress of the relavence between functional roles of retinal miRNAs and the retinal development of vertebrate.

Identification of the binding region for interaction of optineurin with neural retina leucine / 中华实验眼科杂志

Background Gene encoding optineurin (OPTN) is a causative gene for glaucoma and amyotrophic lateral sclerosis,with a more expression in retina.Our previous study isolated OPTN-interacting proteins and identified that the gene encode the basic leucine zipper (bZIP) transcription factor neural retina leucine (NRL) zipper,a causative gene for retinitis pigmentosa,and further study demonstrated the interaction between OPTN and NRL proteins in nuclei of cultured HeLaS3 cells.Objective This study was to determine the protein binding site of OPTN necessary for NRL binding.Methods A deletion series of OPTN-expression plasmids were constructed and co-expressed with hemagglutinin (HA)-tagged NRL in HeLaS3 cells,respectively.The cytoplasmic and nuclear fractions were used to perform co-immunoprecipitate (CoIP) and Western blot with anti-tag antibodies.Results In the nuclear fractions of cells transfected with the del1 st,del2nd or del3rd plasmid,a band of coimmunoprecipitated HA-labelled NRL (HA-NRL) was detected.However,the del4th plasmid did not produce a band.The NRL band was not found in cytoplasmic fractions from transfected cells with any of the deletion plasmids or with the whole-length OPTN plasmid.Conclusions The protein binding site of OPTN necessary for NRL binding is determined.This result demonstrates the binding of Flag-OPTN and HA-NRL in HeLaS3 cells.A series of partial-deletion OPTN plasmids demonstrated that the tail region (423-577 amino acids) of OPTN was necessary for binding with NRL.

Prometeo: regeneración tisular: pifias de la naturaleza y esperanzas de la ciencia / Prometheus: tissue regeneration: natural errors and scientific hope

En el movisimo campo de las células troncales ("stem cell") y la medicina regenerativa, la búsqueda del Santo Grial de la investigación científica, es la recreacion o la inducción del renacimiento de un órgano funcional, llamese hígado, retina o riñon. En un extremo el hígado de Prometeo, de inherente capacidad para regenerarse, la demanda del órgano excede en mucho la disponibilidad de donantes. En Estados Unidos de America, 9% de los pacientes con insuficiencia hepática fallecen a la espera de un trasplante, así que la investigación en tratamientos regenerativos nunca ha tenido más fundamento y adquirido más énfasis que en estos tiempos. En el otro extremo, la retina, inexplicable olvido de la naturaleza, como otras neuronas del sistema nervioso incapaz de regenerarse a sí misma y hasta ahora, inmune a la neuroprotección y reparación después de una injuria. No obstante en un futuro no muy lejano será posible preservar y restaurar la visión en personas en las que se encuentre amenazada o se haya perdido por enfermedad o injuria del nervio óptico

In the newest field of stem cells and regenerative medicine, the quest for the Holy Grail of scientific research is the recreation or induction of rebirth of a functional organism, such as the liver, retina o kidney. At one end liver of Prometheus with its inherent capacity to regenerate, has a demand that greatly exceeds the availability of donors. In the United States of America, 9% of patients with liver failure die waiting for a transplant, so research in regenerative treatment has never had more importance or acquired greater emphasis than at this time. At the other end, the retina, inexplicable oblivion of nature, is, as other neurons of the central nervous system, unable to regenerate itself and so far, immune to neuroprotection and repair after an injury. Nevertheless, in the future it will be possible, however, to preserve and restore vision in people whose optic nerve are threatened or have been lost due to illness or injury

Altered Expression of GLAST and Glutamine Synthetase in the Streptozotocin-induced Diabetic Rat Retina / 대한해부학회지

Diabetic hyperglycemia induces transient ischemia in the neural retina. High level of extracellular glutamate resulting from ischemia, in turn, influences on glutamate homeostasis. The present study has been conducted to clarify the alteration of the glutamate homeostasis-associated substances in the retinal Muller cells in response to a diabetic injury by streptozotocin injection. Young adult Sprague -Dawley rats were injected with streptozotocin (60 mg/kg body weight in 0.05 M sodium citrate buffer, pH 5.5) under anesthesia with 4% chloral hydrate. Animals above 300 mg/dl in blood glucose level were cared for 1, 4, 12 and 24 weeks, respectively. At each time-point, the retinas were dissected out and processed for immuno-histochemical and immunoblotting analyses by using guinea pig anti -GLAST and mouse anti-glutamine synthetase (GS) antibodies. In the normal retina, GLAST and GS were immuno-localized in the Muller cells, the outer plexiform layer (OPL), the border between the inner nuclear layer and the inner plexiform layer (IPL), a band in the middle of the IPL, and the border between the IPL and the ganglion cell layer. The expression of both proteins was decreased remarkably in the OPL by 12 weeks of diabetes and increased slightly in the end feet of the Muller cells from 4 weeks onwards. Immunoblotting results of the two proteins in the diabetic retinas were largely consistent with those of immuno-histochemistry. These results suggest that the alteration of glutamate homeostasis in the diabetic state is initiated mainly in the OPL by decreasing the uptake of glutamate via down-regulated GLAST.

Human embryonic neural retina transplantation to rabbit retina / 眼科新进展

Objective　To evaluate the results of the experimental transplantation of human embryonic neural retina to rabbits.Methods　Neural retina from human embryo of 2.5～3.5 months were transplanted to the site where choroids and retina were excised through posterior sclera in 6 adult rabbits. 20g*L-1 Cyclosporine oil and 1g*L-1 Dexamethasone eyedrops were locally used to control the rejection 3 times a day postoperatively. The transplants were observed under electron-microscope 3 months later.Results　In 5 survival grafts out of 6 cases, the cone and rod cells,a few ganglion cells and relatively a lot of amacrine cells and Muller cells were found under electron-microscope. But the photoreceptors and ganglion cells were immature in development,the synaptic connection was not evident, the inner limiting membrane and nerve fiber layer were not found. The immune cells involved in rejection were not observed.Conclusions　The survival rate of the transplants of the human embryonic neural retinas is relatively high, the differentiation of the grafts is confirmed under electron-microscope, but the development of the neural cells is not good enough to maturity. The rejection is controlled in a good state with Cyclosporine and Dexamethasone locally administrated.