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Intraocular Pressure Induced Retinal Changes Identified Using Synchrotron Infrared Microscopy.

ABSTRACT: Infrared (IR) spectroscopy has been used to quantify chemical and structural characteristics of a wide range of materials including biological tissues. In this study, we examined spatial changes in the chemical characteristics of rat retina in response to intraocular pressure (IOP) elevation using synchrotron infrared microscopy (SIRM), a non-destructive imaging approach. IOP elevation was induced by placing a suture around the eye of anaesthetised rats. Retinal sections were collected onto transparent CaF2 slides 10 days following IOP elevation. Using combined SIRM spectra and chemical mapping approaches it was possible to quantify IOP induced changes in protein conformation and chemical distribution in various layers of the rat retina. We showed that 10 days following IOP elevation there was an increase in lipid and protein levels in the inner nuclear layer (INL) and ganglion cell layer (GCL). IOP elevation also resulted in an increase in nucleic acids in the INL. Analysis of SIRM spectra revealed a shift in amide peaks to lower vibrational frequencies with a more prominent second shoulder, which is consistent with the presence of cell death in specific layers of the retina. These changes were more substantial in the INL and GCL layers compared with those occurring in the outer nuclear layer. These outcomes demonstrate the utility of SIRM to quantify the effect of IOP elevation on specific layers of the retina. Thus SIRM may be a useful tool for the study of localised tissue changes in glaucoma and other eye diseases.

SUBMITTER: Shen HH

PROVIDER: S-EPMC5053542 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Intraocular Pressure Induced Retinal Changes Identified Using Synchrotron Infrared Microscopy.

Shen Hsin-Hui HH Liu Guei-Sheung GS Chow Seong Hoong SH Wang Jiang-Hui JH He Zheng Z Nguyen Christine C Lin Tsung-Wu TW Bui Bang V BV

PloS one 20161006 10

Infrared (IR) spectroscopy has been used to quantify chemical and structural characteristics of a wide range of materials including biological tissues. In this study, we examined spatial changes in the chemical characteristics of rat retina in response to intraocular pressure (IOP) elevation using synchrotron infrared microscopy (SIRM), a non-destructive imaging approach. IOP elevation was induced by placing a suture around the eye of anaesthetised rats. Retinal sections were collected onto tran ...[more]

PMID: 27711151

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Project description:PurposeTo determine the long-term changes in the intraocular pressure (IOP) following vitrectomy for rhegmatogenous retinal detachment (RRD), epiretinal membrane (ERM), and macular hole (MH), and to investigate the relationship between the retinal disease and the incidence of late-onset IOP elevation.MethodsThis was a retrospective, observational, comparative study. We reviewed the medical records of 54 eyes of 54 RRD patients, 117 eyes of 117 ERM patients, and 75 eyes of 75 MH patients who underwent 20-, 23- or 25-gauge vitrectomy. The IOPs before surgery and 1, 3, 6, and 12 months following vitrectomy, and also at the final visit (average, 23.95 months) were evaluated. We defined a significant increase in the IOP as an increase of ?4 mmHg from the preoperative IOP, and this increase was taken to be a 'death' event for the Kaplan-Meier survival analyses.ResultsThe mean follow-up period was not significantly different among the groups. The mean IOP at 3 (P = 0.001) and 12 (P = 0.011) months following the vitrectomy and at the final visit (P = 0.002) were significantly higher than that before the vitrectomy in the RRD group. The mean IOP in the RRD group was significant higher than that in the ERM group at 1 (P = 0.005), 3 (P = 0.009), and 12 (P = 0.013) months following vitrectomy, and at the final visit (P = 0.032). Kaplan-Meier survival analyses showed that the RRD group had a significantly higher risk of an IOP increase following vitrectomy than the other groups (P<0.001 by log-rank test). Multivariate logistic regression analyses showed that a preoperative diagnosis of RRD was the only risk factor that was significantly associated with a postoperative IOP elevation after excluding eyes with a low preoperative IOP (odds ratio, 3.208; P = 0.003).ConclusionsA late-onset IOP elevation following vitrectomy was observed only in eyes that underwent RRD surgery. The elevation was probably caused by the specific characteristics and surgical procedures of RRD. Clinicians should pay more attention to the IOP elevation for long times after vitrectomy especially in eyes with RRD.

Project description:Clinically, a large proportion of glaucoma patients undergo repeated intraocular pressure (IOP) spike (Spike IOP) attacks during their sleep, which may facilitate retinopathy. In this study, we established a mouse model of repeated transient Spike IOP to investigate the direct damage to the retina following Spike IOP attacks, and elucidated the underlying molecular mechanism. We analyzed the changes in the number of retinal ganglion cells (RGCs) via immunofluorescence. Thereafter, we detected retinal cell apoptosis via terminal deoxynucleotidyl transferase deoxyuridine triphosphate (dUTP) nick-end labeling (TUNEL) staining, and performed RNA sequencing (RNA-seq) to reveal the underlying molecular mechanism. Finally, we validated the expression of key molecules in the endoplasmic reticulum (ER) stress pathway using quantitative real-time polymerase chain reaction (qRT-PCR) and western blot analysis. Results revealed a time-dependent RGC loss in Spike IOP, evidenced by a reduction in the number of Brn3a-positive RGCs in experimental eyes following a 7-d continuous treatment with Spike IOP. In addition, TUNEL staining indicated that apoptosis of retinal cells started in the outer nuclear layer (ONL), and then spread to the ganglion cell layer (GCL) with time. RNA-seq analysis revealed that ER stress might be involved in Spike IOP-induced retinal injury. This result was corroborated by western blot, which revealed upregulation of ER stress-related proteins including binding immunoglobulin protein/glucose-regulated protein 78 (BiP/GRP78), phosphorylated inositol-requiring enzyme 1 (p-IRE1), unspliced X-box-binding protein 1 (XBP1-u), spliced X-box-binding protein 1 (XBP1-s), phosphorylated c-Jun N-terminal kinase (p-JNK), C/EBP-homologous protein (CHOP), and B-cell lymphoma 2 (Bcl-2)-associated X protein (Bax). These findings indicate that repeated IOP transients are detrimental to the retina, while ER stress plays an important role in retinal cell apoptosis in this situation. Notably, repeated Spike IOP among glaucoma patients is a crucial factor for progressive retinopathy.

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Project description:Janus kinase (JAK) deregulation of the JAK/signal transducers and activators of transcription pathway leads to myelofibrosis that can be treated by JAK inhibitors including Ruxolitinib and Tofacitinib. Even though both inhibitors are effective against myelofibrosis, each of them has a different mode of action in the cells. Ruxolitinib is an inhibitor for selective JAK1/2, and Tofacitinib is an inhibitor for JAK3. This study evaluated the chemical fingerprints of TF-1 cells after JAK inhibitor treatments by the synchrotron Fourier transform infrared microspectroscopy (S-FTIR) spectrum. Tofacitinib and Ruxolitinib treatments in TF-1 cells were applied with a chemical fingerprint approach in S-FTIR spectroscopy and in vitro cytotoxicity in a cell-based assay. Principal component analysis or PCA was utilized to classify three cell treatments with three biochemical alteration absorbances of lipid vibration by the C-H stretching, protein amide I that appeared from the C=O stretching, and a P=O phosphodiester bond from nucleic acids. The results showed that the inhibition effect of Ruxolitinib on the TF-1 cell lines was two-fold higher than Tofacitinib. PCA distinguishes untreated and drug-treated cells by detecting cellular biochemical alteration. The loading plots identify that proteins and nucleic acids were the different main components in disparate cell treatments. Tofacitinib was distinct from the others in lipid and nucleic acid. The second derivative spectra of the three molecular components had decreased lipid production and accumulation, changes in secondary structures in proteins, and a high level of RNA overexpression in cell treatment. The JAK inhibitors caused different spectroscopic biomarkers of the modifications of secondary protein conformation, stimulated cell lipid accumulation, and phosphorylation from untreated cells. The alteration of cellular biochemical components suggests that FTIR is a potential tool to analyze specific patterns of drug cellular responses at the molecular level.

Dataset Information

Intraocular Pressure Induced Retinal Changes Identified Using Synchrotron Infrared Microscopy.

Publications

Intraocular Pressure Induced Retinal Changes Identified Using Synchrotron Infrared Microscopy.

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