Loss of Gcn2 exacerbates gossypol induced oxidative stress, apoptosis and inflammation in zebrafish.

Gossypol, a naturally occurring compound found in cottonseed meal, shows promising therapeutic potential for human diseases. However, within the aquaculture industry, it is considered an antinutritional factor. The incorporation of cottonseed meal into fish feed introduces gossypol, which induces intracellular stresses and hinders overall health of farmed fish. The aim of this study is to determine the role of General control nonderepressible 2 (gcn2), a sensor for intracellular stresses in gossypol-induced stress responses in fish. In the present study, we established two gcn2 knockout zebrafish lines. A feeding trial was conducted to assess the growth-inhibitory effect of gossypol in both wild type and gcn2 knockout zebrafish. The results showed that in the absence of gcn2, zebrafish exhibited increased oxidative stress and apoptosis when exposed to gossypol, resulting in higher mortality rates. In feeding trial, dietary gossypol intensified liver inflammation in gcn2-/- zebrafish, diminishing their growth and feed conversion. Remarkably, administering the antioxidant N-acetylcysteine (NAC) was effective in reversing the gossypol induced oxidative stress and apoptosis, thereby increasing the gossypol tolerance of gcn2-/- zebrafish. Exposure to gossypol induces more severe mitochondrial stress in gcn2-/- zebrafish, thereby inducing metabolic disorders. These results reveal that gcn2 plays a protective role in reducing gossypol-induced oxidative stress and apoptosis, attenuating inflammation responses, and enhancing the survivability of zebrafish in gossypol-challenged conditions. Therefore, maintaining appropriate activation of Gcn2 may be beneficial for fish fed diets containing gossypol.

Microneedle fractional radiofrequency associated with drug delivery for facial atrophic acne scars and skin rejuvenation.

Microneedle fractional radiofrequency (MFRF) has been used to improve photoaging and scars. This study aimed to evaluate the efficacy and safety of MFRF with basic fibroblast growth factor (bFGF) for facial atrophic acne scars and skin rejuvenation by blinded visual evaluation, self-report, and reflective confocal microscopy (RCM). Fifteen subjects were randomized to the MFRF with bFGF group and fifteen to the MFRF group. All subjects underwent three-session therapy and a follow-up period. Significant group differences were in ECCA, global improvement score, satisfaction, and downtime before and after treatment. Combination therapy could be more effective than monotherapy for acne scars and facial rejuvenation. In addition, RCM can be used to observe the changes in skin collagen before and after treatment in evaluating cosmetic efficacy.

Efficient retinal ganglion cells transduction by retro-orbital venous sinus injection of AAV-PHP.eB in mature mice.

Gene therapy is one of the strategies that may reduce or reverse progressive neurodegeneration in retinal neurodegenerative diseases. However, efficiently delivering transgenes to retinal ganglion cells (RGCs) remains hard to achieve. In this study, we innovatively investigated transduction efficiency of adeno-associated virus (AAV)-PHP.eB in murine RGCs by retro-orbital venous sinus injection. Five doses of AAV-PHP.eB-EGFP were retro-orbitally injected in venous sinus in adult C57/BL6J mice. Two weeks after administration, RGCs transduction efficiency was quantified by retinal flat-mounts and frozen section co-labeling with RGCs marker Rbpms. In addition, safety of this method was evaluated by RGCs survival rate and retinal morphology. To conform efficacy of this new method, AAV-PHP.eB-CNTF was administrated into mature mice through single retro-orbital venous injection after optic nerve crush injury to evaluate axonal elongation. Results indicated that AAV- PHP.eB readily crossed the blood-retina barrier and was able to transduce more than 90% of RGCs when total dose of virus reached 5 × 1010 vector genomes (vg). Moreover, this technique did not affect RGCs survival rate and retinal morphology. Furthermore, retro-orbital venous delivery of AAV-PHP.eB-CNTF effectively transduced RGCs, robustly promoted axonal regeneration after optic nerve crush injury. Thus, novel AAV-PHP.eB retro-orbital injection provides a minimally invasive and efficient route for transgene delivery in treatment of retinal neurodegenerative diseases.

Effect of short-term compression therapy after thermal ablation for varicose veins: study protocol for a prospective, multicenter, non-inferiority, randomized controlled trial.

BACKGROUND: For patients with varicose veins, the goal is to relieve pain and swelling, reduce the severity of edema, improve skin changes, and heal ulcers associated with venous disease. Compression therapy is the cornerstone of their management. Several studies have shown that wearing an elastic bandage for the first 24 h and then a compression stocking for a week can effectively reduce the pain after thermal ablation. However, in clinical practice, patient compliance with this treatment could be better, considering difficulties in pulling up and removing the compression stocking, tightness, and skin irritation because these must be worn for a prolonged period. A potential solution to battling these barriers is short-term compression therapy. Besides, the effect and necessity of wearing compression stockings after thermal ablation have been questioned. Based on current clinical experience and limited evidence, although some scholars have suggested that compression therapy may be an unnecessary adjunctive therapy after thermal ablation, there is still a great deal of uncertainty in the absence of compression therapy after thermal ablation compared to compression therapy. Therefore, we advocate further research to evaluate the clinical effect of short-term postoperative compression therapy. Furthermore, well-designed randomized controlled trials are needed. METHODS: A prospective, multicenter, non-inferiority randomized controlled trial is designed to evaluate the non-inferiority of target vein occlusion rate at 3 months. Three hundred and sixty patients will be randomly assigned in a 1:1 ratio to one of the following treatments: (A) 3 M™ Coban™ elastic bandage for 48 h or (B) 3 M™ Coban™ elastic bandage for the first 24 h and then a class II compression full-length stocking (23-32 mm Hg) for 1 week. The two groups will be compared on several variables, including target vein occlusion rate at 3 months (primary outcome indicator), pain, quality of life, clinical severity of varicose veins, postoperative complications, time to return to regular work, and compliance. DISCUSSION: Suppose the effect of the 3 M™ Coban™ elastic bandage for 48 h proves to be non-inferior to long-term compression therapy. In that case, this short-term treatment may contribute to a future update of clinical guidelines for compression therapy after thermal ablation of varicose veins, resulting in higher patient compliance and better postoperative quality of life. TRIAL REGISTRATION: Clinical Trials NCT05840991 . Registered on May 2023.

Comparison of the efficacy of dienogest and GnRH-a after endometriosis surgery.

OBJECTIVE: To compare the efficacy of dienogest and GnRH-a after endometriosis surgery. METHODS: Patients with endometriosis who were admitted to our hospital from December 2020 to March 2022 were randomly collected. A total of 81 patients were collected and divided into 40 cases in the control group and 41 cases in the observation group. Among them, the control group was treated with GnRH-a drug, and the observation group was treated with dienogest (DNG). RESULTS: The study found that the therapeutic effects of the two drugs were basically the same in patients with endometriosis. The VAS and Kupperman scores of the control group were 0.78 ± 0.8, 3.9 ± 1.84, P < 0.05, respectively; the VAS and Kupperman scores of the observation group were 0.73 ± 0.78, 1.55, respectively ± 1.24, P < 0.05, the difference was statistically significant.In the case of postoperative recurrence, the observation group was better than the control group, with 8 cases of recurrence in the control group and 2 cases of recurrence in the observation group, P < 0.05. CONCLUSION: In the comparison of postoperative efficacy of the two drugs on patients with endometriosis, dienogest is better than GnRH-a adjuvant drug in postoperative recurrence, and has a good improvement and application, which is worthy of further promotion in clinical practice.

Core transcription programs controlling injury-induced neurodegeneration of retinal ganglion cells.

Regulatory programs governing neuronal death and axon regeneration in neurodegenerative diseases remain poorly understood. In adult mice, optic nerve crush (ONC) injury by severing retinal ganglion cell (RGC) axons results in massive RGC death and regenerative failure. We performed an in vivo CRISPR-Cas9-based genome-wide screen of 1,893 transcription factors (TFs) to seek repressors of RGC survival and axon regeneration following ONC. In parallel, we profiled the epigenetic and transcriptional landscapes of injured RGCs by ATAC-seq and RNA-seq to identify injury-responsive TFs and their targets. These analyses converged on four TFs as critical survival regulators, of which ATF3/CHOP preferentially regulate pathways activated by cytokines and innate immunity and ATF4/C/EBPγ regulate pathways engaged by intrinsic neuronal stressors. Manipulation of these TFs protects RGCs in a glaucoma model. Our results reveal core transcription programs that transform an initial axonal insult into a degenerative process and suggest novel strategies for treating neurodegenerative diseases.

Single-layered phase-change metasurfaces achieving efficient wavefront manipulation and reversible chiral transmission.

Efficient control of the phase and polarization of light is of significant importance in modern optics and photonics. However, traditional methods are often accompanied with cascaded and bulky designs that cannot fulfill the ongoing demand for further integrations. Here, a single-layered metasurface composed of nonvolatile phase-change material Ge2Sb2Se4Te1 (GSST) is proposed with tunable spin-orbit interactions in subwavelength scale. According to the spin-dependent destructive or constructive interference, asymmetric transmission for circularly polarized incidence (extinction ratio > 8:1) can be achieved when GSST is in an amorphous state. Moreover, when GSST changes to crystalline state, reversed chiral transmission (extinction ratio > 12:1) can be observed due to the existence of intrinsic chirality. In addition, as the average cross-polarized transmitted amplitude is larger than 85%, arbitrary wavefront manipulations can be achieved in both states simultaneously based on the theory of Pancharatnam-Berry phase. As a proof of concept, several functional metasurface devices are designed and characterized to further demonstrate the validation of our design methodology. It is believed that these multifunctional devices with ultrahigh compactness are promising for various applications including chiroptical spectroscopy, EM communication, chiral imaging, and information encryption.

Structures, Electronic Properties and Carrier Transport Mechanisms of Si Nano-Crystalline Embedded in the Amorphous SiC Films with Various Si/C Ratios.

Recent investigations of fundamental electronic properties (especially the carrier transport mechanisms) of Si nanocrystal embedded in the amorphous SiC films are highly desired in order to further develop their applications in nano-electronic and optoelectronic devices. Here, Boron-doped Si nanocrystals embedded in the amorphous SiC films were prepared by thermal annealing of Boron-doped amorphous Si-rich SiC films with various Si/C ratios. Carrier transport properties in combination with microstructural characteristics were investigated via temperature dependence Hall effect measurements. It should be pointed out that Hall mobilities, carrier concentrations as well as conductivities in films were increased with Si/C ratio, which could be reached to the maximum of 7.2 cm2/V∙s, 4.6 × 1019 cm-3 and 87.5 S∙cm-1, respectively. Notably, different kinds of carrier transport behaviors, such as Mott variable-range hopping, multiple phonon hopping, percolation hopping and thermally activation conduction that play an important role in the transport process, were identified within different temperature ranges (10 K~400 K) in the films of different Si/C ratio. The changes from Mott variable-range hopping process to thermally activation conduction process with temperature were observed and discussed in detail.

Multistate Nonvolatile Metamirrors with Tunable Optical Chirality.

Compared with conventional mirrors that behave as isotropic electromagnetic (EM) reflectors, metamirrors composed of periodically aligned artificial meta-atoms exhibit increased degrees of freedom for EM manipulations. However, the functionality of most metamirrors is fixed by design, and how to achieve active EM control is still elusive. Here, we propose a multistate metamirror based on the nonvolatile phase change material Ge2Sb2Te5 (GST) with four distinct functionalities that can be realized in the infrared region by exploiting the temperature-activated phase transition. When varying the crystallinity of GST, the metamirror has the capability to perform as a right-handed circular polarization chiral mirror, a narrowband achiral mirror, a left-handed circular polarization chiral mirror, or a broadband achiral mirror, respectively. The inner physics is further explained by the construction or cancellation of extrinsic two-dimensional chirality. As a proof of concept, experimental verification is carried out and the measured results agree well with their simulated counterparts. Such a multifunctional tunable metamirror could address a wide range of applications from sensing and spectroscopy to analytical chemistry and imaging.

Biodegradable scaffolds facilitate epiretinal transplantation of hiPSC-Derived retinal neurons in nonhuman primates.

Transplantation of stem cell-derived retinal neurons is a promising regenerative therapy for optic neuropathy. However, significant anatomic differences compromise its efficacy in large animal models. The present study describes the procedure and outcomes of human-induced pluripotent stem cell (hiPSC)-derived retinal sheet transplantation in primate models using biodegradable materials. Stem cell-derived retinal organoids were seeded on polylactic-coglycolic acid (PLGA) scaffolds and directed toward a retinal ganglion cell (RGC) fate. The seeded tissues showed active proliferation, typical neuronal morphology, and electrical excitability. The cellular scaffolds were then epiretinally transplanted onto the inner surface of rhesus monkey retinas. With sufficient graft-host contact provided by the scaffold, the transplanted tissues survived for up to 1 year without tumorigenesis. Histological examinations indicated survival, further maturation, and migration. Moreover, green fluorescent protein-labeled axonal projections toward the host optic nerve were observed. Cryopreserved organoids were also able to survive and migrate after transplantation. Our results suggest the potential efficacy of RGC replacement therapy in the repair of optic neuropathy for the restoration of visual function. STATEMENT OF SIGNIFICANCE: In the present study, we generated a human retinal sheet by seeding hiPSC-retinal organoid-derived RGCs on a biodegradable PLGA scaffold. We transplanted this retinal sheet onto the inner surface of the rhesus monkey retina. With scaffold support, donor cells survive, migrate and project their axons into the host optic nerve. Furthermore, an effective cryopreservation strategy for retinal organoids was developed, and the thawed organoids were also observed to survive and show cell migration after transplantation.

Shot noise of spin-polarized electrons in a single-channel magnetic tunnel junctions.

Based on the free electron approximation and Egues' shot noise theory, the shot noise of spin-polarized electrons tunneling in ferromagnetic/semiconductor/ferromagnetic tunnel junctions is studied. Considering the matching of conduction band between ferromagnetic and semiconductor layers, our results show that the Fano factors of spin-polarized electrons have resonant tunneling characteristics when the semiconductor thickness and Rashba spin-orbit coupling strength are increased. When the magnetic moments in two ferromagnetic layers are parallel, with the increase of the molecular field in the ferromagnets, the Fano factor for spin-up electron decreases to zero and then increases exponentially and the Fano factor for spin-down electron is always linear. But when the magnetic moments are antiparallel, the Fano factors for different spin directions tend to be the same. In addition, the Fano factors for different spin directions are almost zero when the incident electron energy is located in the low energy region, but exhibit irregular oscillation when the incident electron energy is located in the high energy region. At the same time, with the variations of the angle of the magnetic moments in two ferromagnetic layers, the electrons Fano factors for different spin orientations show obvious separation characteristics. On the other hand, the conduction band mismatch between ferromagnetic and semiconductor layers is considered, the Fano factors of electrons with different spin directions show obvious difference compared with the results of conduction band matching.

Reconfigurable Continuous Meta-Grating for Broadband Polarization Conversion and Perfect Absorption.

As promising building blocks for functional materials and devices, metasurfaces have gained widespread attention in recent years due to their unique electromagnetic (EM) properties, as well as subwavelength footprints. However, current designs based on discrete unit cells often suffer from low working efficiencies, narrow operation bandwidths, and fixed EM functionalities. Here, by employing the superior performance of a continuous metasurface, combined with the reconfigurable properties of a phase change material (PCM), a dual-functional meta-grating is proposed in the infrared region, which can achieve a broadband polarization conversion of over 90% when the PCM is in an amorphous state, and a perfect EM absorption larger than 91% when the PCM changes to a crystalline state. Moreover, by arranging the meta-grating to form a quasi-continuous metasurface, subsequent simulations indicated that the designed device exhibited an ultralow specular reflectivity below 10% and a tunable thermal emissivity from 14.5% to 91%. It is believed that the proposed devices with reconfigurable EM responses have great potential in the field of emissivity control and infrared camouflage.

Islet1 and Brn3 Expression Pattern Study in Human Retina and hiPSC-Derived Retinal Organoid.

This study was conducted to determine the dynamic Islet1 and Brn3 (POU4F) expression pattern in the human fetal retina and human-induced pluripotent stem cell- (hiPSC-) derived retinal organoid. Human fetal eyes from 8 to 27 fetal weeks (Fwks), human adult retina, hiPSC-derived retinal organoid from 7 to 31 differentiation weeks (Dwks), and rhesus adult retina were collected for cyrosectioning. Immunofluorescence analysis showed that Islet1 was expressed in retinal ganglion cells in the fetal retina, human adult retina, and retinal organoids. Unexpectedly, after Fwk 20, Brn3 expression gradually decreased in the fetal retina. In the midstage of development, Islet1 was detected in bipolar and developing horizontal cells. As the photoreceptor developed, the Islet1-positive cone precursors gradually became Islet1-negative/S-opsin-positive cones. This study highlights the distinguishing characteristics of Islet1 dynamic expression in human fetal retina development and proposes more concerns which should be taken regarding Brn3 as a cell-identifying marker in mature primate retina.

Dexamethasone Provides Effective Immunosuppression for Improved Survival of Retinal Organoids after Epiretinal Transplantation.

We investigated the efficacy of the immunosuppressants rapamycin (RAP) and dexamethasone (DEX) in improving the survival of retinal organoids after epiretinal transplantation. We first compared the immunosuppressive abilities of DEX and RAP in activated microglia in an in vitro setting. Following this, we used immunofluorescence, real-time polymerase chain reaction, and flow cytometry to investigate the effects of DEX and RAP on cells in the retinal organoids. Retinal organoids were then seeded onto poly(lactic-co-glycolic) acid (PLGA) scaffolds and implanted into rhesus monkey eyes (including a healthy individual and three monkeys with chronic ocular hypertension (OHT) induction) and subjected to different post-operative immunosuppressant treatments; 8 weeks after the experiment, histological examinations were carried out to assess the success of the different treatments. Our in vitro experiments indicated that both DEX and RAP treatments were equally effective in suppressing microglial activity. Although both immunosuppressants altered the morphologies of cells in the retinal organoids and caused a slight decrease in the differentiation of cells into retinal ganglion cells, the organoid cells retained their capacity to grow and differentiate into retinal tissues. Our in vivo experiments indicate that the retinal organoid can survive and differentiate into retinal tissues in a healthy rhesus monkey eye without immunosuppressive treatment. However, the survival and differentiation of these organoids in OHT eyes was successful only with the DEX treatment. RAP treatment was ineffective in preventing immunological rejection, and the retinal organoid failed to survive until the end of 8 weeks. DEX is likely a promising immunosuppressant to enhance the survival of epiretinal implants.

The Effect of Decomposed PbI2 on Microscopic Mechanisms of Scattering in CH3NH3PbI3 Films.

Hybrid organic-inorganic perovskites (HOIPs) exhibit long electronic carrier diffusion length, high optical absorption coefficient, and impressive photovoltaic device performance. At the core of any optoelectronic device lie the charge transport properties, especially the microscopic mechanism of scattering, which must efficiently affect the device function. In this work, CH3NH3PbI3 (MAPbI3) films were fabricated by a vapor solution reaction method. Temperature-dependent Hall measurements were introduced to investigate the scattering mechanism in MAPbI3 films. Two kinds of temperature-mobility behaviors were identified in different thermal treatment MAPbI3 films, indicating different scattering mechanisms during the charge transport process in films. We found that the scattering mechanisms in MAPbI3 films were mainly influenced by the decomposed PbI2 components, which could be easily generated at the perovskite grain boundaries (GBs) by releasing the organic species after annealing at a proper temperature. The passivation effects of PbI2 in MAPbI3 films were investigated and further discussed with emphasis on the scattering mechanism in the charge transport process.

BAM15 attenuates transportation-induced apoptosis in iPS-differentiated retinal tissue.

BACKGROUND: BAM15 is a novel mitochondrial protonophore uncoupler capable of protecting mammals from acute renal ischemic-reperfusion injury and cold-induced microtubule damage. The purpose of our study was to investigate the effect of BAM15 on apoptosis during 5-day transportation of human-induced pluripotent stem (hiPS)-differentiated retinal tissue. METHODS: Retinal tissues of 30 days and 60 days were transported with or without BAM15 for 5 days in the laboratory or by real express. Immunofluorescence staining of apoptosis marker cleaved caspase3, proliferation marker Ki67, and neural axon marker NEFL was performed. And expression of apoptotic-related factors p53, NFkappaB, and TNF-a was detected by real-time PCR. Also, location of ganglion cells, photoreceptor cells, amacrine cells, and precursors of neuronal cell types in retinal tissue was stained by immunofluorescence after transportation. Furthermore, cell viability was assessed by CCK8 assay. RESULTS: Results showed transportation remarkably intensified expression of apoptotic factor cleaved caspase3, p53, NFkappaB, and TNF-a, which could be reduced by supplement of BAM15. In addition, neurons were severely injured after transportation, with axons manifesting disrupted and tortuous by staining NEFL. And the addition of BAM15 in transportation was able to protect neuronal structure and increase cell viability without affecting subtypes cells location of retinal tissue. CONCLUSIONS: BAM15 might be used as a protective reagent on apoptosis during transporting retinal tissues, holding great potential in research and clinical applications.

Tetramethylpyrazine (TMP) ameliorates corneal neovascularization via regulating cell infiltration into cornea after alkali burn.

In the present study, we investigated the underlying mechanism of tetramethylpyrazine (TMP)-medicated inhibition of corneal neovascularization (CNV). Our data showed that TMP could effectively downregulate the expression levels of CXCR4 mRNA and protein, as well as inhibit HUVECs, endothelial cells, tubule formation in vitro. In vivo, alkali burn (1 M NaOH) could remarkably upregulate CXCR4 expression and increase the migration of TNF-α-positive cells to corneal stroma. TMP drops could significantly downregulate CXCR4 expression in cornea, compared to the control. However, there was no difference in the downregulation of CXCR4 between TMP and FK506, an immunosuppressive drug. Moreover, the immunofluorescent staining of CD45 showed TMP and FK506 could significantly restrain the bone marrow (BM)-derived infiltration while the F4/80 staining reflects the suppression of macrophage aggregation. Meanwhile TMP could regulate the Interleukin 10 (IL-10) and FK506 could restrain the Interleukin 2 (IL-2). Furthermore, TMP and FK506 significantly ameliorate corneal opacity and neovascularization. Clinical assessment detected an obvious improvement in TMP and FK506 treatment groups, compared to controls in vivo. Thus, TMP had similar effects in inhibition of immune response and CNV by suppressing BM-infiltrating cells into cornea as FK506. TMP could be a potential agent in eye-drop therapy for cornea damaged by Alkali Burn.

Tetramethylpyrazine in a Murine Alkali-Burn Model Blocks NFκB/NRF-1/CXCR4-Signaling-Induced Corneal Neovascularization.

Purpose: Tetramethylpyrazine (TMP) is the active ingredient extracted from the Chinese herb Chuanxiong. The purpose of our study was to identify the mechanism of therapeutic TMP suppression of pathologic chemokine receptor 4 (CXCR4) transcription. Methods: C57BL/6J mice with alkali-burned corneas were treated with either TMP eye drops (1.5 mg/mL) or PBS. Corneal neovascularization (CNV) was measured and a clinical assessment was made by slit lamp microscopy. Expression of CXCR4 and the transcription factors nuclear respiratory factor-1 (NRF-1), nuclear factor kappa B (NFκB), forkhead box C1, and yin yang 1 were tracked by real-time RT-PCR and immunofluorescence staining of murine corneas. Western blot, real-time PCR, and immunofluorescence evaluated expression of related genes in human umbilical vein endothelial cells (HUVECs) after 200-µmol/L TMP treatment. In addition, plasmid transfection and chromatin immunoprecipitation assays elucidated the relationship among NRF-1, NFκB, and CXCR4. Results: Corneas treated with TMP had smaller areas of neovascularization and scored better in clinical assessments. Injured corneas showed significantly elevated expressions of NRF-1, NFκB, and CXCR4 that were normalized in vivo by TMP treatment. Similarly, in HUVECs in vitro, TMP decreased expression of NRF-1, NFκB, and CXCR4. Overexpression of NFκB or NRF-1 raised the expression of CXCR4 in HUVECs, but not synergistically. Chromatin immunoprecipitation assays detected only NRF-1 bound to the CXCR4 promoter region, suggesting NFκB controls CXCR4 expression by upregulating NRF-1. Together, our data suggest TMP downregulates CXCR4 by repressing NRF-1 expression in CNV, likely indirectly by downregulating NFκB. Conclusions: Our results implicate a novel mechanism wherein TMP inhibits neovascularization via an NFκB/NRF-1/CXCR4 circuit.

Nuclear Respiratory Factor-1 (NRF-1) Regulates Transcription of the CXC Receptor 4 (CXCR4) in the Rat Retina.

Purpose: The CXC receptor 4 (CXCR4) is required for various physiologic and pathologic processes in the eye, including stem cell trafficking, neuronal development, immune responses, and ocular neovascularization. Here, we used the rat retina models to determine the mechanisms driving CXCR4 transcription. Methods: The expression pattern of CXCR4 and nuclear respiratory factor-1 (NRF-1) were profiled in the rat retina during the course of development. Chromatin immunoprecipitation (CHiP) assay determined the transcriptional mechanism of CXCR4 in rat retina. A rat model of oxygen-induced retinopathy (OIR) that mimics retinal ischemia-reperfusion injury was established. Under either normoxic or hypoxic conditions, CXCR4 and NRF-1 expression in rat retinas was tracked by RT-PCR and Western analysis. Immunofluorescence staining localized CXCR4 and NRF-1. Results: Both CXCR4 and NRF-1 were highly expressed in the neonatal rat retina, down-regulated in parallel, and silenced in fully developed retinas (1 month of age). ChIP assays revealed that NRF-1 was required for CXCR4 promoter activity in rat retinas. In the OIR rat model, retinal hypoxia induced up-regulation of CXCR4 and NRF-1 concurrently. Conclusions: Our findings suggest that NRF-1 regulates the expression of CXCR4 in normal retinal development and in pathologic processes of retinal hypoxia and neovascularization.