Interferon-γ induces retinal pigment epithelial cell Ferroptosis by a JAK1-2/STAT1/SLC7A11 signaling pathway in Age-related Macular Degeneration.

Retinal pigment epithelium (RPE) cell damage is implicated in the pathogenesis of age-related macular degeneration (AMD). An increase of interferon-γ (IFN-γ) levels was observed in patients with AMD, but whether inflammatory factors are causally related to AMD progression is unclear. Here, we demonstrate a direct causal relationship between IFN-γ and RPE cell death. IFN-γ induced human retinal pigment epithelial cell (ARPE-19) death accompanied by increases in Fe2+ , reactive oxygen species, lipid peroxidation, and glutathione (GSH) depletion, which are main characteristics of ferroptosis. Mechanistically, IFN-γ upregulates the level of intracellular Fe2+ through inhibiting Fe2+ efflux protein SLC40A1 and induces GSH depletion by blocking cystine/glutamate antiporter, System xc-. At the same time, treatment with IFN-γ decreases the level of glutathione peroxidase 4 (GPx4), rendering the cells more sensitive to ferroptosis. JAK1/2 and STAT1 inhibitors could reverse the reduction of SLC7A11, GPx4 and GSH expression induced by IFN-γ, indicating IFN-γ induces ARPE-19 cell ferroptosis via activation of the JAK1-2/STAT1/SLC7A11 signaling pathway. The above results were largely confirmed in IFN-γ-treated mice in vivo. Finally, we used sodium iodate (NaIO3 )-induced retinal degeneration to further explore the role of ferroptosis in AMD in vivo. Consistent with the role of IFN-γ, treatment with NaIO3 decreased SLC7A11, GPx4 and SLC40A1 expressions. NaIO3 -induced RPE damage was accompanied by increased iron, lipid peroxidation products (4-hydroxynonenal, malondialdehyde), and GSH depletion, and ferroptosis inhibitors could reverse the above phenomenon. Taken together, our findings suggest that inhibiting ferroptosis or reducing IFN-γ may serve as a promising target for AMD.

Displacement of the retina after idiopathic macular hole surgery with different internal limiting membrane peeling patterns.

AIM: To explore retinal displacement after surgical treatment for idiopathic macular hole (IMH) with different internal limiting membrane (ILM) peeling patterns. METHODS: Totally 22 eyes from 20 patients with IMH were randomly allocated into two groups, N-T group (11 eyes) and T-N group (11 eyes). For patients in N-T group, ILM was peeled off from nasal to temporal retina. For patients in T-N group, ILM was peeled off from temporal to nasal retina. Preoperative, postoperative 1, 3, and 6mo, autofluorescence fundus images were collected for manual measurement of distances of fixed nasal (N), temporal (T), superior (S), and inferior (I) retinal points (bifurcation or crossing of retinal vessels) around the macula to the optic disc (OD). These were respectively defined as N-OD, T-OD, S-OD, and I-OD. The retinal displacement, macular hole closure rate, and best corrected visual acuity (BCVA) were compared between the two groups after surgery. RESULTS: At postoperative 1, 3, and 6mo, the macula slipped toward the OD, manifested by the decreased T-OD, N-OD, S-OD, and I-OD (P<0.05). No significant difference was found in the T-OD, N-OD, S-OD, and I-OD between N-T group and T-N group. IMH closure rate was 100% both in N-T group and T-N group. There was no significant difference in BCVA between two groups (P<0.05). CONCLUSION: The macula slips toward the OD after successful macular hole surgery. The two different ILM peeling pattern show similar visual outcome and retinal displacement, which means ILM peeling directions are not the influencing factor of postoperative retinal displacement.

The complete chloroplast genome of Solanum betacea (Solanaceae, Solaneae).

Solanum betacea is a sub-tropical tree, and the fruit has high nutritional value, unique flavor and color. It is used as a functional ingredient in health care, food, cosmetic and pharmaceutical applications. The complete chloroplast(Cp) genome of S. betacea has been assembled and annotated in this paper. Its length was 155,937 bp, containing a large single-copy region of 86,731 bp, a small single-copy region of 18,450 bp, and a pair of IR regions of 25,378 bp in each. The complete chloroplast genome of S. betacea contained 134 genes, including 90 protein-coding genes, 36 transfer RNA genes (tRNAs), and 8 ribosome RNA genes (rRNAs). The overall GC content was 37.7% and the GC contents of the LSC, SSC, and IR regions were 35.7%, 31.8%, and 43.1%, respectively. Phylogenetic analysis with the reported chloroplast genomes revealed that S. betacea has been most closely related to Solanum torvum. These findings will provide useful information for further investigation of chloroplast genome evolution in Solanum betacea.

The complete chloroplast genome of Crateva unilocularis (Capparaceae).

Crateva unilocularis is naturally distributed in Southern China, which is an elite natural tree with high edible and medicinal value. In this study, whole chloroplast (cp) genome of Crateva unilocularis was assembled and characterized on the basis of Illumina pair-end sequencing data. The complete cp genome was 156,417 bp in length, containing a large single-copy region (LSC) of 85,607 bp and a small single-copy region (SSC) of 18,164 bp, which were separated by a pair of 26,323 bp inverted repeat regions (IRs). The genome contained 128 genes, including 85 protein-coding genes, 35 tRNA genes, and 8 rRNA genes. The overall GC content is 36.32%, while the corresponding values of the LSC, SSC, and IR regions were 33.98, 29.45, and 42.48%, respectively. The maximum-likelihood phylogenetic analysis showed a strong sister relationship with Crateva tapia. These findings provide a foundation for further investigation of cp genome evolution in Crateva unilocularis and other higher plants.

The complete chloroplast genome of Fraxinus malacophylla (Oleaceae, Oleoideae).

Fraxinus malacophylla is one of the commonly used ecological restoration tree species in rocky desertification areas. It has high medicinal and timber value. And has high marketization prospects. The complete chloroplast genome sequence of F. malacophylla was generated by de novo assembly using whole-genome next generation sequencing. The complete chloroplast genome of F. malacophylla was 155621 bp in total sequence length and divided into four distinct regions: large single copy region (86404 bp), small single copy region (17821 bp), and a pair of inverted repeat regions (25698 bp). The F. malacophylla chloroplast genome annotation predicted a total of 131 genes, consisting of 35 tRNA genes, 8 rRNA genes, and 88 protein-coding genes. Phylogenetic analysis with the reported chloroplast genomes revealed that F. malacophylla has most closely related to F. excelsior.

[Correlation of behavioral performance with expressions of substance P and neurokinin-1 receptor in the L5－S2 spinal cord of chronic prostatitis rats].

OBJECTIVE: To investigate the correlation between the behavioral performance and the expressions of substance P (SP) and neurokinin-1 receptor (NK-1R) in the posterior horn of the L5－S2 spinal cord in rats with chronic prostatitis (CP). METHODS: A CP model was made in 30 adult male SD rats by intraperitoneal injection of 0.5 ml dyphtheria pertussis tetanus (DPT) vaccine and mixed solution of 1 ml prostatein extract and complete adjuvant in a 1∶1 ratio, and another 10 rats were injected with the same volume of normal saline as controls. At 45 (n = 10), 60 (n = 10) and 90 days (n = 10) after modeling, the behavioral changes of the rats were observed by open-field and sucrose consumption tests, the prostatic indexes and levels of serum TNF-α, IL-1ß, IL-2 and IL-10 were obtained, and the expressions of SP and NK1-R in the L5－S2 spinal cord were determined by immunohistochemistry. RESULTS: Compared with the controls, the CP model rats showed obviously decreased horizontal and vertical movement scores and sucrose consumption, particularly in the 90 d group (P < 0.05), significantly reduced prostatic indexes in the 45 d, 60 d and 90 d groups (all P < 0.05), even lower in the 90 d than in the 45 d and 60 d groups (P < 0.05). Edema and lymphocytes were increased in the prostatic tissue with the prolonged time of modeling. The levels of serum TNF-α, IL-1ß, IL-2 and IL-10 were markedly elevated in all the CP rats as compared with those in the controls (P < 0.05), and so were the expressions of SP and NK-1R in the L5－S2 spinal cord (P < 0.05), even more significantly in the 90 d than in the 45 d and 60 d groups (P < 0.05). CONCLUSIONS: Rats with chronic prostatitis are characterized by behavioral manifestation of depression, increased levels of serum TNF-α, IL-1ß, IL-2 and IL-10, and a time-dependent upregulation of the expressions of SP and NK-1R in the posterior horn of the L5-S2 spinal cord, which suggests a correlation between the behavioral performance and the expressions of SP and NK-1R in the L5－S2 spinal cord of the rats.

[Expressions of SP and NK-1R increase in the posterior horn of the L5－S2 spinal cord in rats with chronic nonbacterial prostatitis].

OBJECTIVE: To investigate the expressions of substance P (SP) and neurokinin-1 receptor (NK-1R) in the posterior horn of the L5－S2 spinal cord in the rat model of chronic nonbacterial prostatitis (CNP) at different time points of modeling. METHODS: Forty adult male SD rats were randomly divided into four groups of equal number, control, 45 d model, 60 d model, and 90 d model, and proteins were obtained from the prostatic tissue of another 30 rats. The CNP model was made by intraperitoneal injection of 0.5 ml DPT vaccineand intradermal injection of mixed solution of 1 ml prostatein extract and complete adjuvant at a 1∶1 ratio, while the control rats were injected with the same volume of normal saline. At 45, 60, and 90 days after modeling, we measured the paw withdrawal threshold (PWT) of the rats, determined the levels of TNF-α, IL-1ß, IL-2, and IL-10 in the prostate tissue by ELISA, observed the histomorphological changes in the prostate by transmission electron and light microscopy, and detected the expressions of SP and NK1-R in the L5－S2 spinal cord by immunohistochemistry. RESULTS: The model rats showed significantly increased sensitivity to pain, with remarkably lowered PWT at 45, 60, and 90 days after modeling. The levels of TNF-α, IL-1ß, IL-2, and IL-10 in the prostate tissue were markedly elevated in the CNP models as compared with those in the controls (all P<0.05), most significantly at 90 days (all P<0.05). Immunohistochemistry showed that the expressions of SP and NK-1R were remarkably higher in the CNP model groups than in the control (all P<0.05), the highest at 90 days. Light microscopy revealed no inflammatory cell infiltration in the prostate tissue of the control rats, and obvious edema and increased lymphocytes were observed with the prolonged time of modeling.Transmission electron microscopy showed inflammatory changes in the prostate tissue of the model rats and that peritubular interstitial edema was most obvious at 90 days, with widened intervals between peritubular cells and the epithelial base and increased numbers of fibroblasts and collagen fibrils. CONCLUSIONS: The synthesis of SP and the level of NK-1R were increased in the posterior horn of the L5－S2 spinal cord in the rat model of CNP.