Impact of Prophylactic Ranibizumab to Prevent Neovascular Age-Related Macular Degeneration on Eyes With Intermediate Age-Related Macular Degeneration.

Purpose: The purpose of this study was to determine the impact of prophylactic ranibizumab (PR) injections given every 3 months in eyes with intermediate nonexudative age-related macular degeneration (AMD) on drusen volume, macular layer thicknesses, and progression of geographic atrophy (GA) area over 24 months in the PREVENT trial. Methods: This post hoc analysis of the prospective PREVENT trial compared eyes with intermediate AMD randomized to PR versus sham injections to determine rates of conversion to neovascular AMD over 24 months. Drusen area and volume, macular thickness and volume, and retinal layer thicknesses were measured on spectral-domain optical coherence tomography images and analyzed. Masked grading of GA area and subretinal drusenoid deposits (SDDs) using fundus autofluorescence images was performed. Results: There were no statistical differences in drusen area and volumes between groups, and similar reductions in central subfield thickness, mean cube thickness, cube volume, and retinal sublayer thickness from baseline to 24 months (P = 0.018 to < 0.001), with no statistical differences between groups in any of these anatomic parameters. These findings were not impacted by the presence or absence of SDD. Among the 9 eyes with GA in this study, mean GA growth rate from baseline to 24 months was 1.34 +/- 0.79 mm2/year after PR and 1.95 +/- 1.73 mm2/year in sham-treated eyes (P = 0.49), and similarly showed no statistical difference with square root transformation (P = 0.61). Conclusions: Prophylactic ranibizumab given every 3 months did not appear to affect drusen volume, macular thinning, or GA progression in eyes with intermediate AMD. Translational Relevance: This work investigates the impact of PR on progressive retinal degeneration in a clinical trial.

Prophylactic Ranibizumab to Prevent Neovascular Age-Related Macular Degeneration in Vulnerable Fellow Eyes: A Randomized Clinical Trial.

PURPOSE: To determine whether prophylactic ranibizumab prevents the development of neovascular age-related macular degeneration (nAMD) in eyes with intermediate age-related macular degeneration (AMD) for patients with preexisting nAMD in their contralateral eye. DESIGN: Multicenter randomized clinical trial. PARTICIPANTS: Adults aged 50 years and older with intermediate AMD (multiple intermediate drusen [≥63 µm and <125 µm] or ≥1 large drusen [≥125 µm] and pigmentary changes) in the study eye and nAMD in the contralateral eye. INTERVENTION: Intravitreal ranibizumab injection (0.5 mg) or sham injection every 3 months for 24 months. MAIN OUTCOME MEASURES: Conversion to nAMD over 24 months (primary). Change in best-corrected visual acuity from baseline to 24 months (secondary). RESULTS: Among 108 enrolled participants (54 [50%] in each group), all except 2 were non-Hispanic Whites, 61 participants (56%) were female, and the mean age was 78 years. The mean baseline visual acuity was 77.7 letters (Snellen equivalent 20/32). Conversion to nAMD over 24 months occurred among 7 of 54 eyes (13%) in both groups (ranibizumab vs. sham hazard ratio = 0.91 [95% confidence interval (CI), 0.32-2.59]; P = 0.86). At 24 months, the cumulative incidence of nAMD adjusted for loss to follow-up was 14% (95% CI, 4%-23%) in the ranibizumab group and 15% (95% CI, 4%-25%) in the sham group. At 24 months, the mean change in visual acuity from baseline was -2.1 letters (standard deviation, 5.4 letters) with ranibizumab and -1.4 letters (standard deviation, 7.7 letters) with sham (adjusted difference = -0.8 letters [95% CI, -3.7 to 2.2 letters]; P = 0.62). The proportion of eyes that lost at least 10 letters of visual acuity from baseline at 24 months was 2 of 39 (5%) with ranibizumab and 4 of 40 (10%) with sham. There were no serious ocular adverse events in either group. CONCLUSIONS: Quarterly dosing of 0.5 mg ranibizumab in eyes with intermediate AMD did not reduce the incidence of nAMD compared with sham injections; however, the study was likely underpowered given the 95% CI, and a clinically meaningful effect cannot be excluded. There also was no effect on visual acuity at 24 months. Other strategies to reduce neovascular conversion in these vulnerable eyes are needed.

Meticulous multimodal analysis of aflibercept therapy for submacular vascularized pigment epithelial detachment associated with neovascular AMD in a prospective case series, the EVEN study.

PURPOSE: This prospective case series investigates the visual and anatomical outcomes including detailed volumetrics of eyes with vascularized pigment epithelial detachments (PED) treated with aflibercept in eyes with neovascular age-related macular degeneration (nAMD) through meticulous analysis in a reading center setting. METHODS: We conducted a single-arm multicenter, prospective, open-labeled, interventional case series, comparing visual and anatomic outcomes at 12 months with baseline for intense aflibercept therapy. Eyes with submacular vascularized PED due to AMD received 2.0 mG of intravitreal aflibercept at baseline and then monthly for 6 months. During the subsequent 6 months, mandatory aflibercept therapy was given for every other month, while additional aflibercept injections were allowed between mandatory injections if necessary, at 4 weeks after last injection, contingent on pre-defined visual and anatomic re-treatment criteria. Standardized ETDRS vision measurement, anterior and posterior segment examination, and high-density spectral-domain optical coherence tomography scans were obtained at baseline and monthly, while fundus photography and fluorescein angiography were obtained at baseline, 3,6, and 12 months. Indocyanine-green angiography was obtained at baseline and 3 months. Meticulous multidimensional assessment of the scanned multimodal serial images was then performed by Doheny Image Reading Center. RESULTS: Of 36 eyes and patients with mean age of 80, mean baseline and 12-month-ETDRS BCVA was 59 ± 8.9 letters (20/66), and 65 ± 27 letters (20/50), respectively; (6.5 letters improvement, p = 0.02). Significant reductions from baseline to month-12 were noted for multiple anatomic measures, including PED maximum height, entire lesion and central 1-mm subfield of PED mean thickness and volume, and mean subretinal hyperreflective material (SHRM) thickness and volume, also entire lesion of retinal thickness, retinal volume, and mean subretinal fluid (SRF) thickness (mean reductions in magnitude ranging from 37.5 to 91.7%, all p < 0.001). FA measurements also showed significant decrease from baseline to month-12, including area and greatest linear diameter (GLD) of fibrovascular PED, area and GLD of NV area and leakage (mean reductions in magnitude from 41.9 to 87.7%, p value from 0.002 to <0.001). This case series shows that while majority of reductions in SRF volume occurred during first month from baseline, majority of reduction in retinal, PED, and SHRM volumes occurred during first 2 months after onset of anti-VEGF injections. RPE tears developed in 5 eyes (13.9%) correlating with eyes with large PED height and volume at baseline (mean height >800 µm, mean volume >4 mm3). Geographic atrophy (GA) was noted in only 1 eye at baseline, but in 16 eyes (44.4%) by 12 months. CONCLUSIONS AND IMPORTANCE: Significant improvement in vision and anatomic measures including volumetrics of vPED were noted at 12 months after aflibercept therapy. Besides substantial PED height, large PED volume at baseline also correlated with RPE tears in 13.9% of eyes with vPED after anti-VEGF therapy. Reduction in SHRM correlated directly with decrease in PED, and more than 40% of study eyes developed GA by 12 months following intense anti-VEGF therapy.

Three-Year Findings on Intraocular Pressure Changes in The Prospective Retinal and Optic Nerve Vitrectomy Evaluation (PROVE) Study.

BACKGROUND AND OBJECTIVE: This paper reports 3-year intraocular pressure (IOP) outcomes of the Prospective Retinal and Optic Nerve Vitrectomy Evaluation (PROVE) study. PATIENTS AND METHODS: The prospective, controlled, observational study included 80 eyes of 40 participants undergoing routine pars plana vitrectomy. Study patients underwent preoperative evaluation and multimodal testing of the study (surgical) and fellow (control) eye. This testing was repeated at 3 months postoperatively and then annually for 3 years. RESULTS: Thirty-two of 40 patients (80%) completed 3-year follow-up. At 3 years postoperatively, there was no difference in IOP measurements in surgical eyes overall from baseline (P = .36). Subgroup analysis of pseudophakic eyes at baseline showed a significant elevation in IOP from 14.3 mm Hg ± 2.9 mm Hg at baseline to 16.8 mm Hg ± 3.2 mm Hg at 3-year follow-up (P < .029). Fellow eyes did not experience a significant change from baseline. CONCLUSION: The authors' 3-year results show that IOP is consistently and significantly elevated in pseudophakic eyes compared to baseline following routine vitrectomy. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:371-376.].

TYPE 1 VERSUS TYPE 3 NEOVASCULARIZATION IN PIGMENT EPITHELIAL DETACHMENTS ASSOCIATED WITH AGE-RELATED MACULAR DEGENERATION AFTER ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY: A Prospective Study.

PURPOSE: To evaluate the response to aflibercept therapy for Type 1 and Type 3 neovascularization in pigment epithelial detachments associated with treatment-naive, neovascular age-related macular degeneration. METHODS: In this multicentered, prospective study, eligible eyes underwent an intravitreal aflibercept injection protocol for 12 months. Visual acuity and morphologic features of the pigment epithelial detachments were compared at baseline and follow-up intervals between eyes with Type 1 versus Type 3 neovascularization. RESULTS: Thirty-six eyes were analyzed. At 12 months, Type 1 lesions showed a 4.5 ± 23 Early Treatment of Diabetic Retinopathy Study letter improvement (P = 0.1665) versus a 14 ± 11 (P = 0.0072) letter improvement with Type 3 lesions. Both Type 1 and 3 eyes showed a significant decrease in pigment epithelial detachment size, subretinal fluid, and subretinal hyperreflective material; however, Type 3 eyes had a greater reduction in pigment epithelial detachment size and subretinal hyperreflective material, as well as a reduction in central retinal thickness. Type 1 eyes required an average of 1.636 (range, 1-4) injections to resolve fluid, which was greater than Type 3 eyes, which required an average of 1.143 (range, 1-2) injections (P = 0.0251). CONCLUSION: Intravitreal aflibercept injections were efficacious for pigment epithelial detachments, but baseline and follow-up anatomical and functional outcomes differed in Type 1 versus Type 3 neovascularization. The better response of Type 3 eyes with fewer injections suggests that differentiation of the neovascularization subtype at the initial diagnosis may allow for a more tailored, optimal therapy.

VANISHING RETINAL DETACHMENT.

PURPOSE: The purpose of this report is to describe a case of rhegmatogenous retinal detachment in the setting of chronic kidney disease that exhibited complete retinal reattachment after serial hemodialysis. METHODS: Retrospective case report. RESULTS: A 58-year-old woman with acute vision loss was found to have a macula-involving rhegmatogenous retinal detachment. Due to chronic kidney disease, she continued with routinely scheduled hemodialysis for 1 week until surgical clearance was obtained. Preoperative examination revealed complete reattachment of the retina with a persistent retinal tear. Barrier laser was applied to the tear and the retina remained attached until the most recent follow-up 8 months later. The workup of alternate etiologies was unrevealing. CONCLUSION: This case describes a temporal association between hemodialysis and resolution of subretinal fluid due to rhegmatogenous retinal detachment. A potential causal linkage is suggested based on shifting fluid dynamics associated with hemodialysis. A shift in treatment paradigm is not advised.

Prospective Retinal and Optic Nerve Vitrectomy Evaluation (PROVE) study: twelve-month findings.

PURPOSE: To report 1-year outcomes of the Prospective Retinal and Optic Nerve Vitrectomy Evaluation study. DESIGN: Prospective, controlled, observational study. PARTICIPANTS: Eighty eyes of 40 participants undergoing pars plana vitrectomy for epiretinal membrane (ERM), macular hole (MH), or vitreous opacities. METHODS: Enrolled participants underwent baseline evaluation of the study (surgical) and fellow (control) eyes by a masked fellowship-trained glaucoma specialist; evaluation included intraocular pressure (IOP; Goldmann applanation and Tono-Pen), central corneal thickness, gonioscopy, and cup-to-disc ratio measurement. Baseline testing included bilateral color fundus and optic disc photography, fundus autofluorescence, automated perimetry, and optical coherence tomography (OCT) of the macula and optic nerve. Evaluations were repeated at 3 months and 1 year after surgery. MAIN OUTCOME MEASURES: The primary outcome measure was changes in peripapillary retinal nerve fiber layer (pRNFL) thickness. Secondary outcomes included changes in macular thickness and IOP. RESULTS: Thirty-eight of 40 patients completed 1 year of follow-up. Mean visual acuity (VA) improved in study eyes from baseline (P = 0.003) but remained worse than fellow eyes (P<0.001). Study eyes had thinner inferior pRNFL thickness (114±16.8 µm) compared with fellow eyes (123±14.7 µm; P = 0.004). Mean IOP difference between study eyes and fellow eyes increased from baseline to 1 year. At 1 year, MH study eyes had higher mean IOP (16.0±3.7 mmHg) compared with fellow eyes (14.8±3.4 mmHg; P = 0.08). Mean IOP for pseudophakic study eyes increased from 14.5±3.2 mmHg at baseline to 16.0±2.8 mmHg at 1 year (P = 0.04). Central subfield thickness (CST) and cube volume decreased in study eyes at 1 year but remained greater than that of fellow eyes (P<0.05). Reduction in CST from baseline correlated with degree of VA improvement (P<0.05). Mean deviation (MD) improved in ERM study eyes at 1 year when compared with baseline (-2.2 vs. -4.0; P = 0.02) but remained worse than fellow eyes (-1.2; P = 0.002). CONCLUSIONS: One year after vitrectomy, VA, CST, and MD improved in study eyes but not to the level of fellow eyes. Inferior pRNFL thickness decreased in study eyes. Reduction in CST from baseline correlated with degree of VA improvement. Pseudophakic study eyes demonstrated increased IOP when compared with baseline.

Prospective Retinal and Optic Nerve Vitrectomy Evaluation (PROVE) study: findings at 3 months.

BACKGROUND: The purpose of this paper is to report the 3-month findings of the Prospective Retinal and Optic Nerve Vitrectomy Evaluation (PROVE) study. METHODS: Eighty eyes of 40 participants undergoing vitrectomy were enrolled. Participants underwent baseline evaluation of the study (surgical) and fellow (control) eye that included: intraocular pressure, central corneal thickness, gonioscopy, cup-to-disc ratio measurement, color fundus and optic disc photography, automated perimetry, and optical coherence tomography of the macula and optic nerve. Evaluation was repeated at 3 months. Main outcome measures were changes in macula and retinal nerve fiber layer (RNFL) thickness and intraocular pressure. RESULTS: All participants completed follow-up. Mean cup-to-disc ratio of study and fellow eyes at baseline was 0.43 ± 0.2 and 0.46 ± 0.2, respectively, and 13% of participants had undiagnosed narrow angles. There was no significant change in intraocular pressure, cup-to-disc ratio, or pattern standard deviation in study eyes compared with baseline or fellow eyes at 3 months. Vision improved in all study eyes at 3 months compared with baseline (P = 0.013), but remained significantly worse than fellow eyes (P < 0.001). Central subfield and temporal peripapillary RNFL thickness were significantly greater in eyes with epiretinal membrane (P < 0.05), and resolution after surgery correlated with visual improvement (P < 0.05). CONCLUSION: The 3-month results do not indicate any increased risk for open-angle glaucoma but suggest that a relatively high percentage of eyes may be at risk of angle closure glaucoma. Temporal RNFL thickness and central subfield were increased in eyes with epiretinal membrane, and resolution correlated with degree of visual recovery.

Acute macular neuroretinopathy: an atypical case.

PURPOSE: The purpose of this report is to describe extensive acute macular neuroretinopathy lesions with atypical features. METHODS: Retrospective case report. RESULTS: A patient developed acute macular neuroretinopathy in the setting of multiple previously described associations including a flu-like illness, sympathomimetic exposure, overdose of norepinephrine reuptake inhibitors, anemia, thrombocytopenia, and hypotensive shock. The fundus lesions superficially resembled retinal hemorrhages in color and fluorescein angiography pattern. The lesions could be detected on autofluorescence and infrared imaging. Optical coherence tomography revealed outer plexiform layer opacification and photoreceptor abnormalities. CONCLUSION: This case suggests a compounding effect of factors associated with acute macular neuroretinopathy, possible exacerbating insults and outer plexiform layer abnormalities that may correlate with the temporal course of this condition.

Increased prostaglandin E2 (PGE2) levels in proliferative diabetic retinopathy, and correlation with VEGF and inflammatory cytokines.

PURPOSE: We determined vitreous levels of prostaglandin E2 (PGE(2)), VEGF, and 15 other cytokines in diabetic and nondiabetic patients undergoing vitrectomy. METHODS: Of 26 eyes of 26 patients enrolled consecutively, 13 eyes underwent vitrectomy for complications related to proliferative diabetic retinopathy, and the other 13 for epiretinal membrane, macular hole, vitreous opacities, or dislocated intraocular lens. Undiluted vitreous samples were taken at the time of surgery and frozen immediately at -80°C, and later analyzed for PGE(2), VEGF, and 15 other cytokines. RESULTS: PGE(2) levels were 53% higher in diabetic eyes. Mean ± standard deviation PGE(2) levels were 25.11 ± 11 pg/mL and 16.40 ± 7 pg/mL in diabetic and nondiabetic eyes, respectively (P < 0.03). Mean ± standard deviation VEGF levels were 2225 ± 3798 pg/mL and 66 ± 185 pg/mL in diabetic and nondiabetic eyes, respectively (P < 0.001). Other cytokines, including eotaxin-1, growth related oncogene (GRO), interleukin (IL)-6, IL-8, interferon-γ-inducible protein of 10 kDa (IP-10), monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor alpha (TNF-α), and platelet-derived growth factor-AA, also were elevated significantly in diabetic eyes. A significant correlation was seen between PGE(2) levels and IP-10 and VEGF (P = 0.04). CONCLUSIONS: PGE(2) levels are significantly higher in the vitreous of patients with complications from proliferative diabetic retinopathy, and correlate with IP-10 and VEGF. The results of our study suggest that PGE(2) may have a pathogenic role in diabetic retinopathy and implicates a potential therapeutic role for nonsteroidal anti-inflammatory drugs. (ClinicalTrials.gov number, NCT01609881.).

Influence of previous vitrectomy on incidence of macular oedema after cataract surgery in diabetic eyes.

PURPOSE: To evaluate the effect of previous vitrectomy on the incidence of macular oedema (MO) after cataract surgery in diabetic eyes. METHODS: Ninety phakic eyes of 70 patients with diabetes undergoing non-emergent vitrectomy surgery were reviewed for rates of postvitrectomy MO, cataract formation and postcataract surgery MO. Preoperative and final best-corrected visual acuity were recorded. Baseline risk characteristics were analysed. RESULTS: Postvitrectomy MO increases initially but then levels off at 28% by 4 years. Cumulative proportion of eyes requiring cataract surgery after vitrectomy climbs steadily, reaching 40% at 4 years and 60% at 8 years. Of those eyes which underwent vitrectomy and then subsequent cataract surgery, the incidence of postvitrectomy MO was 6% at 6 months, and that of postcataract surgery MO was 30% at 6 months (p<0.02). Previous clinically significant macular oedema (CSMO) predicted development of postcataract surgery MO (p<0.04). CONCLUSIONS: Previous vitrectomy does not appear to lessen rates of postcataract surgery MO. Cataract formation is common after vitrectomy in diabetic eyes, and risk of postcataract surgery MO is substantial and more likely in eyes with prior CSMO. Cataract formation and risk of postcataract surgery MO should be considered when assessing the long-term benefits of vitrectomy surgery in patients with diabetes.

Long-term trends in intraocular pressure after pars plana vitrectomy.

PURPOSE: To evaluate the effect of vitrectomy on intraocular pressure (IOP). METHODS: Retrospective cohort study. Medical records of 101 eyes of 101 patients undergoing nonemergent vitrectomy were reviewed for rates of open-angle glaucoma, increased IOP of >4 mmHg from baseline, change in IOP from baseline, and cataract formation. Preoperative and last measured IOPs were recorded. Baseline risk characteristics including lens status and diabetes were analyzed. Main outcome measures were 1) incidence of open-angle glaucoma; 2) increase in IOP of >4 mmHg; and 3) change in IOP. RESULTS: Mean follow-up was 49 months (range, 12-105 months). Mean baseline IOP was 15.3 mmHg, and mean final IOP was 15.8 mmHg (P = 0.3). At the most recent examination, 35 study eyes had a decrease in IOP from baseline, while 14 eyes had no change and 52 eyes had an increase in IOP. Four study eyes were newly diagnosed with ocular hypertension. No study eye developed open-angle glaucoma or required medical, laser, or surgical treatment for glaucoma. Incidence of increased IOP of >4 was 7% at 4 years and 34% at 8 years. Subgroup analysis of 66 patients comparing study eyes with nonvitrectomized fellow eyes demonstrated no significant difference in rates of increased IOP of >4 (P = 0.85). Neither diabetes nor pseudophakia was associated with significantly increased IOP. CONCLUSION: In this series, vitrectomy does not appear to increase IOP even after removal of the crystalline lens.

Visual function-specific perimetry to identify glaucomatous visual loss using three different definitions of visual field abnormality.

PURPOSE: To compare the most recent versions of standard automated perimetry (SAP), short-wavelength automated perimetry (SWAP), and frequency-doubling technology (FDT) using three definitions of visual field (VF) abnormality: single-test abnormality, abnormality confirmed by the same test, and abnormality confirmed by a different test. METHODS: Data obtained from one eye of each of 174 patients with glaucoma and 164 age-matched healthy control subjects from the Diagnostic Innovations in Glaucoma Study and African Descent and Glaucoma Evaluation Study were included, based on the appearance of the optic disc on stereophotographs. Each participant had two reliable 24-2 SAP-SITA, SWAP-SITA, and Matrix FDT tests. Receiver operating characteristic (ROC) curves were generated for the PSD of each test to equate the tests at 90% and 95% specificity. SAP, SWAP, and FDT were compared under each definition of VF abnormality by assessing the sensitivities, the agreement between tests and the overlap in deficit location at these set specificities. The tests were also compared using the machine-derived PSD. RESULTS: At a set specificity of 95%, single-test sensitivities of 30% (SAP), 29% (SWAP), and 28% (FDT) were observed (all P > 0.05). Sensitivities ranged from 24% to 27% (all P > 0.05) when same-test confirmation was used and from 20% to 23% (all P > 0.05) when different-test confirmation was used. SAP/SAP sensitivity was higher than all different-test combinations (all P < 0.05), and SWAP/FDT sensitivity was lower than all same-test combinations (all P < 0.05). CONCLUSIONS: Confirming VF abnormality is important and optimal when an abnormal SAP is confirmed by a subsequent SAP or SWAP test.

Baseline optical coherence tomography predicts the development of glaucomatous change in glaucoma suspects.

PURPOSE: To assess whether baseline retinal nerve fiber layer (RNFL) measurements obtained with optical coherence tomography (OCT2; Carl Zeiss Meditec, Dublin, California, USA) are predictive of the development of glaucomatous change. DESIGN: Cohort study. METHODS: Participants were recruited from the University of California, San Diego (UCSD) longitudinal Diagnostic Innovations in Glaucoma Study (DIGS). One eye was studied from each of 114 glaucoma suspects with normal standard automated perimetry (SAP) and OCT RNFL imaging at baseline. The cohort was divided into two groups based on the development of glaucomatous change (repeatable abnormal visual fields and/or a change in the stereophotographic appearance of the optic disk). Cox proportional hazards models were used to determine the predictive ability of OCT RNFL thickness measurements. RESULTS: Over a 4.2-year average follow-up period, 23 eyes (20%) developed glaucomatous changes and 91 (80%) did not. At baseline, thinner RNFL measurements, higher SAP pattern standard deviation (PSD), "glaucoma" stereophotograph assessment, and thinner central corneal thickness (CCT) were associated with the study endpoints in univariate analysis. After adjusting for age, intraocular pressure (IOP), CCT, and PSD in multivariate models, a 10 mum thinner average, superior and inferior RNFL at baseline was predictive of glaucomatous change [hazard ratio (95% CI); 1.51 (1.11 to 2.12), 1.57 (1.17 to 2.18), and 1.49, (1.19 to 1.91), respectively]. Results were consistent when stereophotographic assessment was included in multivariate analysis. CONCLUSIONS: Thinner OCT RNFL measurements at baseline were associated with development of glaucomatous change in glaucoma suspect eyes. RNFL thinning was an independent predictor of the glaucomatous change, even when adjusting for stereophotograph assessment, age, IOP, CCT, and PSD.

Co-expression of heat shock transcription factors 1 and 2 in rat retinal ganglion cells.

Heat shock protein (HSP) plays an important role in the maintenance of neuronal survival during harmful conditions. Previously, we reported that metabolic stress induces HSP72 in retinal ganglion cells (RGCs) and protects against excitotoxicity, hypoxia and experimental glaucoma. To understand heat shock protein transcriptional mechanisms, we examined the cellular expression of heat shock factors 1 (HSF1) and 2 (HSF2) in the unstressed adult rat retina. Western blotting, immunohistochemistry and RT-PCR showed that mRNA and protein of HSF1 and HSF2 were present in the rat retina and predominantly expressed in RGC layer cells. Western blotting of dissociated RGC suspensions harvested with Thy-1 immuno-labeled magnetic beads confirmed that RGCs expressed HSF1, HSF2 and HSP72. Our findings suggest that both heat shock transcription factors 1 and 2 are linked to the heat shock response in retinal ganglion cells.