PURPOSE: To evaluate the surgical success of rectus muscle plication compared to resection and to compare the short- and long-term changes in ocular alignment after both procedures. METHODS: The medical records of all patients who underwent a rectus muscle tightening procedure (resection or plication) at a single institution over a 5-year period by a single surgeon were reviewed retrospectively. Binocular alignment was recorded before and immediately after surgery and again at 6-12 weeks and final follow-up visit. Primary outcome was surgical success rate, defined as distance alignment of ≤10(Δ) for horizontal and ≤6(Δ) for vertical strabismus. Secondary outcomes were reoperation rate and postoperative alignment drift. RESULTS: A total of 72 surgeries were identified for inclusion: 48 resections and 24 plications. Surgical success was significantly higher in the resection group than in the plication group (89% vs 58%; P = 0.005) at both 6-12 weeks' follow-up (P = 0.005) and at mean final follow-up of 19 ± 13 months (range, 3-56 months [n = 48]; P = 0.03). Reoperations were performed in 3 patients in the plication group (12.5%), all for undercorrection; there were no reoperations in the resection group (P = 0.03). CONCLUSIONS: Rectus muscle plication has many potential advantages over resection, including sparing of the ciliary circulation. In our experience, however, patients treated with plication had lower surgical success rates and a higher reoperation rate. Surgeons should monitor their long-term results before considering plication as their procedure of choice over resection.
Purpose: The purpose of this study is to assess cone-mediated central retinal function in children with a history of preterm birth, including subjects with and without retinopathy of prematurity (ROP). The multifocal electroretinogram (mfERG) records activity of the postreceptor retinal circuitry. Methods: mfERG responses were recorded to an array of 103 hexagonal elements that subtended 43° around a central fixation target. The amplitude and latency of the first negative (N1) and first positive (P1) response were evaluated in six concentric rings centered on the fovea. Responses were recorded from 40 subjects with a history of preterm birth (severe ROP, mild ROP, no ROP) and 19 term-born control subjects. Results: The amplitude of N1 and P1 varied significantly with eccentricity and ROP severity. For all four groups, these amplitudes were largest in the center and decreased with eccentricity. At all eccentricities, N1 amplitude was significantly smaller in severe ROP and did not differ significantly among the other three groups (mild ROP, no ROP, term-born controls). P1 amplitude in all preterm groups was significantly smaller than in controls; P1 amplitude was similar in no ROP and mild ROP and significantly smaller in severe ROP. Conclusions: These results provide evidence that premature birth alone affects cone-mediated central retinal function and that the magnitude of the effect varies with severity of the antecedent ROP. The lack of difference in mfERG amplitude between the mild and no ROP groups is evidence that the effect of ROP on the neurosensory retina may not depend solely on appearance of abnormal retinal vasculature.
Aung T, Ozaki M, Lee MC, Schlötzer-Schrehardt U, Thorleifsson G, Mizoguchi T, Igo RP, Haripriya A, Williams SE, Astakhov YS, Orr AC, Burdon KP, Nakano S, Mori K, Abu-Amero K, Hauser M, Li Z, Prakadeeswari G, Bailey JCN, Cherecheanu AP, Kang JH, Nelson S, Hayashi K, Manabe S-I, Kazama S, Zarnowski T, Inoue K, Irkec M, Coca-Prados M, Sugiyama K, Järvelä I, Schlottmann P, Lerner FS, Lamari H, Nilgün Y, Bikbov M, Park KH, Cha SC, Yamashiro K, Zenteno JC, Jonas JB, Kumar RS, Perera SA, Chan ASY, Kobakhidze N, George R, Vijaya L, Do T, Edward DP, de Juan Marcos L, Pakravan M, Moghimi S, Ideta R, Bach-Holm D, Kappelgaard P, Wirostko B, Thomas S, Gaston D, Bedard K, Greer WL, Yang Z, Chen X, Huang L, Sang J, Jia H, Jia L, Qiao C, Zhang H, Liu X, Zhao B, Wang Y-X, Xu L, Leruez S, Reynier P, Chichua G, Tabagari S, Uebe S, Zenkel M, Berner D, Mossböck G, Weisschuh N, Hoja U, Welge-Luessen U-C, Mardin C, Founti P, Chatzikyriakidou A, Pappas T, Anastasopoulos E, Lambropoulos A, Ghosh A, Shetty R, Porporato N, Saravanan V, Venkatesh R, Shivkumar C, Kalpana N, Sarangapani S, Kanavi MR, Beni AN, Yazdani S, Lashay A, Naderifar H, Khatibi N, Fea A, Lavia C, Dallorto L, Rolle T, Frezzotti P, Paoli D, Salvi E, Manunta P, Mori Y, Miyata K, Higashide T, Chihara E, Ishiko S, Yoshida A, Yanagi M, Kiuchi Y, Ohashi T, Sakurai T, Sugimoto T, Chuman H, Aihara M, Inatani M, Miyake M, Gotoh N, Matsuda F, Yoshimura N, Ikeda Y, Ueno M, Sotozono C, Jeoung JW, Sagong M, Park KH, Ahn J, Cruz-Aguilar M, Ezzouhairi SM, Rafei A, Chong YF, Ng XY, Goh SR, Chen Y, Yong VHK, Khan MI, Olawoye OO, Ashaye AO, Ugbede I, Onakoya A, Kizor-Akaraiwe N, Teekhasaenee C, Suwan Y, Supakontanasan W, Okeke S, Uche NJ, Asimadu I, Ayub H, Akhtar F, Kosior-Jarecka E, Lukasik U, Lischinsky I, Castro V, Grossmann RP, Megevand GS, Roy S, Dervan E, Silke E, Rao A, Sahay P, Fornero P, Cuello O, Sivori D, Zompa T, Mills RA, Souzeau E, Mitchell P, Wang JJ, Hewitt AW, Coote M, Crowston JG, Astakhov SY, Akopov EL, Emelyanov A, Vysochinskaya V, Kazakbaeva G, Fayzrakhmanov R, Al-Obeidan SA, Owaidhah O, Aljasim LA, Chowbay B, Foo JN, Soh RQ, Sim KS, Xie Z, Cheong AWO, Mok SQ, Soo HM, Chen XY, Peh SQ, Heng KK, Husain R, Ho S-L, Hillmer AM, Cheng C-Y, Escudero-Domínguez FA, González-Sarmiento R, Martinon-Torres F, Salas A, Pathanapitoon K, Hansapinyo L, Wanichwecharugruang B, Kitnarong N, Sakuntabhai A, Nguyn HX, Nguyn GTT, Nguyn TV, Zenz W, Binder A, Klobassa DS, Hibberd ML, Davila S, Herms S, Nöthen MM, Moebus S, Rautenbach RM, Ziskind A, Carmichael TR, Ramsay M, Álvarez L, García M, González-Iglesias H, Rodríguez-Calvo PP, Cueto LF-V, Oguz Ç, Tamcelik N, Atalay E, Batu B, Aktas D, Kasım B, Wilson RM, Coleman AL, Liu Y, Challa P, Herndon L, Kuchtey RW, Kuchtey J, Curtin K, Chaya CJ, Crandall A, Zangwill LM, Wong TY, Nakano M, Kinoshita S, den Hollander AI, Vesti E, Fingert JH, Lee RK, Sit AJ, Shingleton BJ, Wang N, Cusi D, Qamar R, Kraft P, Pericak-Vance MA, Raychaudhuri S, Heegaard S, Kivelä T, Reis A, Kruse FE, Weinreb RN, Pasquale LR, Haines JL, Thorsteinsdottir U, Jonasson F, Allingham RR, Milea D, Ritch R, Kubota T, Tashiro K, Vithana EN, Micheal S, Topouzis F, Craig JE, Dubina M, Sundaresan P, Stefansson K, Wiggs JL, Pasutto F, Khor CC. Genetic association study of exfoliation syndrome identifies a protective rare variant at LOXL1 and five new susceptibility loci. Nat Genet 2017;Abstract
Exfoliation syndrome (XFS) is the most common known risk factor for secondary glaucoma and a major cause of blindness worldwide. Variants in two genes, LOXL1 and CACNA1A, have previously been associated with XFS. To further elucidate the genetic basis of XFS, we collected a global sample of XFS cases to refine the association at LOXL1, which previously showed inconsistent results across populations, and to identify new variants associated with XFS. We identified a rare protective allele at LOXL1 (p.Phe407, odds ratio (OR) = 25, P = 2.9 × 10(-14)) through deep resequencing of XFS cases and controls from nine countries. A genome-wide association study (GWAS) of XFS cases and controls from 24 countries followed by replication in 18 countries identified seven genome-wide significant loci (P < 5 × 10(-8)). We identified association signals at 13q12 (POMP), 11q23.3 (TMEM136), 6p21 (AGPAT1), 3p24 (RBMS3) and 5q23 (near SEMA6A). These findings provide biological insights into the pathology of XFS and highlight a potential role for naturally occurring rare LOXL1 variants in disease biology.
PurposeThe purpose of the study was to investigate nailfold microvascular morphology in exfoliation syndrome with or without glaucoma (XFS/XFG) compared with primary open-angle glaucoma (POAG) and control subjects using nailfold capillary videomicroscopy.Patients and methodsWe used a JH-1004 capillaroscope to perform nailfold capillary videomicroscopy on the fourth and fifth digit of the non-dominant hand. We enrolled 56 XFS/XFG patients, 87 POAG patients, and 75 control subjects. Masked observers graded the videos for hemorrhages, avascular zones ≥200 microns (μm), and degree of microvascular tortuosity on a four-point subjective scale. Multivariable odds ratios, 95% confidence intervals and P-for trends for assessing the relation between morphological changes and POAG or XFS/XFG were obtained from logistic regression analyses. We also assessed this relation with XFS/XFG compared with POAG in multivariable models.ResultsAfter adjusting for multiple covariates, nailfold hemorrhages, avascular zones ≥200 μm, and higher degree of vascular tortuosity were more common in XFS/XFG vs controls (P-for trend ≤0.0001) and in POAG vs controls (P-for trend ≤0.01). For each 100 capillaries, the number of hemorrhages was similar (P-for trend=0.91) between XFS/XFG and POAG patients; however, there were more avascular zones per 100 capillaries with borderline significance (P-for trend=0.04) in the XFS/XFG group. XFS/XFG patients had more tortuosity than POAG patients; specifically, having a tortuosity score ≥1.5 was associated with a 4.4-fold increased odds of XFS/XFG (95% confidence interval: 1.5-13.3) relative to a tortuosity score <1.0 (P-for trend=0.005).ConclusionA high degree of nailfold capillary tortuosity is a distinct non-ocular feature associated with XFS/XFG compared with either POAG or controls.
PURPOSE: To compare the diagnostic capability of 3-dimensional (3D) neuroretinal rim parameters with existing 2-dimensional (2D) neuroretinal and retinal nerve fiber layer (RNFL) thickness rim parameters using spectral domain optical coherence tomography (SD-OCT) volume scans. MATERIALS AND METHODS: Design: Institutional prospective pilot study. STUDY POPULATION: 65 subjects (35 open-angle glaucoma patients, 30 normal patients). OBSERVATION PROCEDURES: One eye of each subject was included. SD-OCT was used to obtain 2D RNFL thickness values and 5 neuroretinal rim parameters [ie, 3D minimum distance band (MDB) thickness, 3D Bruch's membrane opening-minimum rim width (BMO-MRW), 3D rim volume, 2D rim area, and 2D rim thickness]. MAIN OUTCOME MEASURES: Area under the receiver operating characteristic curve values, sensitivity, and specificity. RESULTS: Comparing all 3D with all 2D parameters, 3D rim parameters (MDB, BMO-MRW, rim volume) generally had higher area under the receiver operating characteristic curve values (range, 0.770 to 0.946) compared with 2D parameters (RNFL thickness, rim area, rim thickness; range, 0.678 to 0.911). For global region analyses, all 3D rim parameters (BMO-MRW, rim volume, MDB) were equal to or better than 2D parameters (RNFL thickness, rim area, rim thickness; P-values from 0.023 to 1.0). Among the three 3D rim parameters (MDB, BMO-MRW, and rim volume), there were no significant differences in diagnostic capability (false discovery rate >0.05 at 95% specificity). CONCLUSIONS: 3D neuroretinal rim parameters (MDB, BMO-MRW, and rim volume) demonstrated better diagnostic capability for primary and secondary open-angle glaucomas compared with 2D neuroretinal parameters (rim area, rim thickness). Compared with 2D RNFL thickness, 3D neuroretinal rim parameters have the same or better diagnostic capability.
Importance: A randomized clinical trial comparing fluocinolone acetonide implant vs systemic corticosteroids and immunosuppression for treatment of severe noninfectious intermediate, posterior, and panuveitides did not result in a significant difference in visual acuity at 2 and 4.5 years; longer-term outcomes are not known. Objective: To compare the association between intravitreous fluocinolone acetonide implant vs systemic therapy and long-term visual and other outcomes in patients with uveitis. Design, Setting, and Participants: Nonprespecified 7-year observational follow-up of the Multicenter Uveitis Steroid Treatment (MUST) randomized clinical trial comparing the alternative treatments. Follow-up was conducted in tertiary uveitis subspecialty practices in the United States (21), the United Kingdom (1), and Australia (1). Of 255 patients 13 years or older with intermediate, posterior, or panuveitis (active within ≤60 days) enrolled in the MUST trial between December 6, 2005, and December 9, 2008, 215 consented to ongoing follow-up through at least 7 years postrandomization (last visit, February 10, 2016). Interventions: Participants had been randomized to receive a surgically placed intravitreous fluocinolone acetonide implant or systemic corticosteroids supplemented by immunosuppression. When both eyes required treatment, both eyes were treated. Main Outcomes and Measures: Primary outcome was change from baseline in best-corrected visual acuity in uveitic eyes (5 letters = 1 visual acuity chart line; potential range of change in letters read, -121 to +101; minimal clinically important difference, 7 letters), analyzed by treatment assignment accounting for nonindependence of eyes when patients had 2 uveitic eyes. Secondary outcomes included potential systemic toxicities of corticosteroid and immunosuppressive therapy and death. Results: Seven-year data were obtained for 161 uveitic eyes (70% of 90 patients assigned to implant) and 167 uveitic eyes (71% of 90 patients assigned to systemic therapy) (77% female; median age at enrollment, 48 [interquartile range, 36-56] years). Change in mean visual acuity from baseline (implant, 61.7; systemic therapy, 65.0) through 7 years (implant, 55.8; systemic therapy, 66.2) favored systemic therapy by 7.2 (95% CI, 2.1-12) letters. Among protocol-specified, prospectively collected systemic adverse outcomes, the cumulative 7-year incidence in the implant and systemic therapy groups, respectively, was less than 10%, with the exceptions of hyperlipidemia (6.1% vs 11.2%), hypertension (9.8% vs 18.4%), osteopenia (41.5% vs 43.1%), fractures (11.3% vs 18.6%), hospitalization (47.6% vs 42.3%), and antibiotic-treated infection (57.4% vs 72.3%). Conclusions and Relevance: In 7-year extended follow-up of a randomized trial of patients with severe intermediate, posterior, or panuveitis, those randomized to receive systemic therapy had better visual acuity than those randomized to receive intravitreous fluocinolone acetonide implants. Study interpretation is limited by loss to follow-up. Trial Registration: clinicaltrials.gov Identifier: NCT00132691.
PurposeTo describe the long-term surgical outcomes of four patients treated for retinal detachment using Seprafilm as a novel technique.MethodsRetinal breaks in four eyes were covered with Seprafilm using a transvitreal approach after cataract surgery, pars plana vitrectomy, fluid-air exchange, and laser photocoagulation. Neither long-standing gas nor silicone oil was used. The patients were not instructed to maintain a specific head positioning postoperatively.ResultsSuccessful retinal reattachment was achieved with a single surgery in all four eyes, and none developed proliferative vitreoretinopathy. The mean best-corrected visual acuity preoperatively and 9 years postoperatively were 20/97 and 20/33, respectively. The intraocular pressure increased several days postoperatively that lasted no longer than 2 weeks. Visual field defects either in the inferonasal or inferotemporal quadrant were detected postoperatively. The mean electroretinogram a- and b-wave amplitude ratios of the operated eyes to the fellow eyes were 0.68 and 0.64 preoperatively and 0.87 and 0.92 postoperatively, respectively. The mean corneal endothelial cell density was 2365 cells/mm(2) preoperatively and 2592 cells/mm(2) postoperatively.ConclusionCovering retinal breaks with Seprafilm may promote retinal reattachment without gas tamponade and postoperative head positioning. The visual outcomes 9 years postoperatively showed no apparent adverse effects of intraocular application of Seprafilm.
Identifying genes required by pathogens during infection is critical for antimicrobial development. Here, we use a Monte Carlo simulation-based method to analyse high-throughput transposon sequencing data to determine the role of infection site and co-infecting microorganisms on the in vivo 'essential' genome of Staphylococcus aureus. We discovered that co-infection of murine surgical wounds with Pseudomonas aeruginosa results in conversion of ∼25% of the in vivo S. aureus mono-culture essential genes to non-essential. Furthermore, 182 S. aureus genes are uniquely essential during co-infection. These 'community dependent essential' (CoDE) genes illustrate the importance of studying pathogen gene essentiality in polymicrobial communities.
PURPOSE: Adequate access to subspecialty care is of concern to patients and physicians alike. One measure of availability is the wait time for cosmetic procedures. The authors investigated geographical differences in wait times for cosmetic upper eyelid blepharoplasty of American Society of Ophthalmic Plastic and Reconstructive Surgery members across the country.
METHODS: This study surveyed all 533 American Society of Ophthalmic Plastic and Reconstructive Surgery members' practices in the United States based on the publically available contact information (www.asoprs.org). Scripted telephone calls were made requesting self-referred cosmetic upper eyelid blepharoplasty. Wait times until the first available appointment and time until the first available surgery date were collected.
RESULTS: Of the membership, 387 (72.6% response rate) respondents offered appointments for cosmetic upper eyelid blepharoplasty. Overall, 84.2% of respondents were male. Practice breakdown was 83.4% in private practice and 16.5% in academic practice. Median wait time until the next available appointment was 14 days (mean 21.2 days, 0-205 days; p = 0.145). Private practice wait time was shorter than academic (median 14 vs. 18 days, mean 19.7 vs. 28.9 days; p =0.004). However, there was wide variability based on region.
CONCLUSIONS: Patients seeking cosmetic upper eyelid blepharoplasty have good access to care by American Society of Ophthalmic Plastic and Reconstructive Surgery members. There are variabilities based on academic versus private practice. Further study can evaluate whether similar findings exist for medically necessary functional procedures. This information may help assess the need for additional practitioners.
PURPOSE: To differentiate the plasma metabolomic profile of patients with age related macular degeneration (AMD) from that of controls, by Nuclear Magnetic Resonance (NMR) spectroscopy. METHODS: Two cohorts (total of 396 subjects) representative of central Portugal and Boston, USA phenotypes were studied. For each cohort, subjects were grouped according to AMD stage (early, intermediate and late). Multivariate analysis of plasma NMR spectra was performed, followed by signal integration and univariate analysis. RESULTS: Small changes were detected in the levels of some amino acids, organic acids, dimethyl sulfone and specific lipid moieties, thus providing some biochemical information on the disease. The possible confounding effects of gender, smoking history and age were assessed in each cohort and found to be minimal when compared to that of the disease. A similar observation was noted in relation to age-related comorbidities. Furthermore, partially distinct putative AMD metabolite fingerprints were noted for the two cohorts studied, reflecting the importance of nutritional and other lifestyle habits in determining AMD metabolic response and potential biomarker fingerprints. Notably, some of the metabolite changes detected were noted as potentially differentiating controls from patients diagnosed with early AMD. CONCLUSION: For the first time, this study showed metabolite changes in the plasma of patients with AMD as compared to controls, using NMR. Geographical origins were seen to affect AMD patients´ metabolic profile and some metabolites were found to be valuable in potentially differentiating controls from early stage AMD patients. Metabolomics has the potential of identifying biomarkers for AMD, and further work in this area is warranted.
We examined the evolutionary history of leading multidrug resistant hospital pathogens, the enterococci, to their origin hundreds of millions of years ago. Our goal was to understand why, among the vast diversity of gut flora, enterococci are so well adapted to the modern hospital environment. Molecular clock estimation, together with analysis of their environmental distribution, phenotypic diversity, and concordance with host fossil records, place the origins of the enterococci around the time of animal terrestrialization, 425-500 mya. Speciation appears to parallel the diversification of hosts, including the rapid emergence of new enterococcal species following the End Permian Extinction. Major drivers of speciation include changing carbohydrate availability in the host gut. Life on land would have selected for the precise traits that now allow pathogenic enterococci to survive desiccation, starvation, and disinfection in the modern hospital, foreordaining their emergence as leading hospital pathogens.
In this issue of Neuron, Aldiri et al. (2017) present an analysis of epigenetic changes during retinal development, and use these data to probe reprogramming of retinal iPSC cells, as well as the origin of retinoblastoma cells.
An apprenticeship model has traditionally been used in procedural and surgical teaching. As the pressures of work hours and patient outcome monitoring increase, surgical teachers need a more flexible plan for teaching procedural skills. We attempt to delineate a program of preprocedural, intraprocedural, and postprocedural teaching that can be used in the field of ophthalmology to maximize a resident's skill acquisition in a constructive learning environment. We review the literature on surgical teaching from within ophthalmology as well as other surgical fields and combine this with teaching experience in an ophthalmic surgical training program to produce a collection of procedural teaching guidelines. These guidelines are structured to serve in both individual teaching settings and in curriculum design.
PURPOSE: To examine the efficacy and safety of infliximab therapy in the treatment for noninfectious intermediate uveitis resistant to conventional immunomodulatory therapy. METHODS: Forty-four eyes of 23 patients with resistant noninfectious intermediate uveitis who were treated with infliximab infusions for a minimum period of 3 months were included. Demographic data, clinical data, and fluorescein angiography and optical coherence tomography findings were collected from the Massachusetts Eye Research and Surgery Institution database between August 2005 and February 2014. Clinical response, improvement in ancillary test findings, and major side effects were evaluated. RESULTS: Nineteen patients (82.6%) achieved remission. The mean duration of treatment to induce remission was 3.99 ± 3.06 months (range, 2-14.7). Cystoid macular edema was the only complication observed during the course of the treatment in 1 eye (2.27%). One patient (4.3%) developed major side effects. None of the patients developed central or peripheral demyelinating neuropathies or multiple sclerosis. At 6 months after remission, logarithm of the minimum angle of resolution visual acuity (P = 0.006) and central macular thickness (P = 0.03) showed significant improvement in patients who achieved remission. CONCLUSION: A significant number of patients achieved remission on infliximab therapy. The incidence of major side effects in our cohort was low.
PURPOSE: To study methods and adverse events of postoperative, sedated suture adjustment after strabismus surgery in the post-anesthesia care unit (PACU). METHODS: We reviewed the postoperative experience of all children ≤18 years of age undergoing adjustable suture strabismus surgery at Boston Children's Hospital over a 3-year period. Time in the hospital, adverse events, and surgical outcomes were reviewed to evaluate safety and healthcare resource utilization. RESULTS: Of 356 patients, 113 required suture adjustment in the PACU, including 24 adjusted while awake and 89 adjusted under sedation. For sedation, sequential boluses of propofol were administered until adjustment was complete. Complete data from the sedated adjustment was available in 76 patients. The median initial bolus was 30 mg; the median total propofol rate was 273 mcg/kg/min. Twelve patients (16%) required only a single bolus of propofol. Of remaining 64 patients, median time from initial to final propofol dose was 7 minutes. Median anesthesiologist time in the PACU was 13 minutes. In the sedated adjustment group, there were no clinically significant adverse events, and the pain score never exceeded 6 (of a possible 10). Median duration of PACU stay was shortest in the group not requiring adjustment. CONCLUSIONS: Sedated suture adjustment allows for fine-tuning of postoperative binocular alignment in children and uncooperative adults. No adverse events were observed in our study group, but the procedure does increase the time patients spend in the hospital. This work will inform disclosure of risks and benefits of sedated adjustment while allowing for more accurate assessment of the cost and quality of adjustable sutures in children.
Stem cell-based disease modeling is an emerging technology for the mechanistic study and therapeutic screening of complex ocular pathologies. In this issue of Cell Stem Cell, Saini et al. (2017) show that iPSC-derived RPE cells from age-related macular degeneration patients express increased levels of pro-inflammatory factors that can be normalized by the anti-aging drug nicotinamide.
Reactive remodeling of optic nerve head astrocytes is consistently observed in glaucoma and other optic nerve injuries. However, it is unknown whether this reactivity is beneficial or harmful for visual function. In this study, we used the Cre recombinase (Cre)-loxP system under regulation of the mouse glial fibrillary acidic protein promoter to knock out the transcription factor signal transducer and activator of transcription 3 (STAT3) from astrocytes and test the effect this has on reactive remodeling, ganglion cell survival, and visual function after experimental glaucoma and nerve crush. After injury, STAT3 knockout mice displayed attenuated astrocyte hypertrophy and reactive remodeling; astrocytes largely maintained their honeycomb organization and glial tubes. These changes were associated with increased loss of ganglion cells and visual function over a 30-day period. Thus, reactive astrocytes play a protective role, preserving visual function. STAT3 signaling is an important mediator of various aspects of the reactive phenotype within optic nerve astrocytes.
Phagocytosis of daily shed photoreceptor outer segments is an important function of the retinal pigment epithelium (RPE) and it is essential for retinal homeostasis. RPE dysfunction, especially impairment of its phagocytic ability, plays an essential role in the pathogenesis of age-related macular degeneration (AMD). Statins, or HMG CoA (3-hydroxy-3-methylglutaryl-coenzyme A) reductase inhibitors, are drugs with multiple properties that have been extensively used to treat hyperlipidemia. However, their effect on RPE cells has not been fully elucidated. Here we report that high dose atorvastatin increased the phagocytic function of ARPE-19 cells, as well as rescue the cells from the phagocytic dysfunction induced by cholesterol crystals and oxidized low-density lipoproteins (ox-LDL), potentially by increasing the cellular membrane fluidity. Similar effects were observed when evaluating two other hydrophobic statins, lovastatin and simvastatin. Furthermore, atorvastatin was able to block the induction of interleukins IL-6 and IL-8 triggered by pathologic stimuli relevant to AMD, such as cholesterol crystals and ox-LDL. Our study shows that statins, a well-tolerated class of drugs with rare serious adverse effects, help preserve the phagocytic function of the RPE while also exhibiting anti-inflammatory properties. Both characteristics make statins a potential effective medication for the prevention and treatment of AMD.