Synucleinopathies, such as Parkinson’s disease and diffuse Lewy body disease, are progressive neurodegenerative disorders characterized by selective neuronal death, abnormal accumulation of misfolded α-synuclein, and sustained microglial activation. In addition to inducing neuronal toxicity, higher-ordered oligomeric α-synuclein causes proinflammatory responses in the brain parenchyma by triggering microglial activation, which may exacerbate pathogenic processes by establishing a chronic neuroinflammatory milieu. Here, we found that higher-ordered oligomeric α-synuclein induced a proinflammatory microglial phenotype by directly engaging the heterodimer TLR1/2 (Toll-like receptor 1 and 2) at the cell membrane, leading to the nuclear translocation of NF-κB (nuclear factor κB) and the increased production of the proinflammatory cytokines TNF-α and IL-1β in a MyD88-dependent manner. Blocking signaling by the TLR1/2 heterodimer with the small molecule inhibitor, CU-CPT22, reduced the expression and secretion of these inflammatory cytokines from cultured primary mouse microglia. Candesartan cilexetil, a drug approved for treating hypertension and that inhibits the expression of TLR2, reversed the activated proinflammatory phenotype of primary microglia exposed to oligomeric α-synuclein, supporting the possibility of repurposing this drug for synucleinopathies.
Purpose: To compare the clinical outcomes of diffractive multifocal and monofocal lenses in post-laser in situ keratomileusis (LASIK) patients who underwent cataract surgery. Methods: This was a retrospective, comparative study of clinical outcomes that was conducted at a referral medical center. Post-LASIK patients who underwent uncomplicated cataract surgery and received either diffractive multifocal or monofocal lens were studied. Visual acuities were compared at baseline and postoperatively. The intraocular lens (IOL) power was calculated with Barrett True-K Formula only. Results: At baseline, both groups had comparable age, gender, and an equal distribution hyperopic and myopic LASIK. A significantly higher percentage of patients receiving diffractive lenses achieved uncorrected distance visual acuity (UCDVA) of 20/25 or better (80 of 93 eyes, 86% vs. 36 of 82 eyes, 43.9%, P = 1.0 x 10 5 ) and uncorrected near vision of J1 or better (63% vs. 0) compared to the monofocal group. The residual refractive error had no significant difference (0.37 ± 0.39 vs. 0.44 ± 0.39, respectively, P = 0.16) in these two groups. However, more eyes in the diffractive group achieved UCDVA of 20/25 or better with residual refractive error of 0.25–0.5 D (36 of 42 eyes, 86% vs. 15 of 24 eyes, 63%, P = 0.032) or 0.75–1.5 D (15 of 21 eyes, 23% vs. 0 of 22 eyes, P = 1.0 x 10 −5 ) compared to the monofocal group. Conclusion: This pilot study shows that patients with a history of LASIK who undergo cataract surgery with a diffractive multifocal lens are not inferior to those who receive monofocal lens. Post-LASIK patients with diffractive lens are more likely to achieve not only excellent near vision, but also potentially better UCDVA, regardless of the residual refractive error.
Infectious keratitis is a devastating cause of vision loss worldwide. Cutibacterium acnes (C. acnes), a commensal bacterium of the skin and ocular surface, is an underrecognized but important cause of bacterial keratitis. This review presents the most comprehensive and up-todate information for clinicians regarding the risk factors, incidence, diagnosis, management, and prognosis of C. acnes keratitis (CAK). Risk factors are similar to those of general bacterial keratitis and include contact lens use, past ocular surgery, and trauma. The incidence of CAK may be approximately 10%, ranging from 5% to 25% in growth-positive cultures. Accurate diagnosis requires anaerobic blood agar and a long incubation period ($7 days). Typical clinical presentation includes small (,2 mm) ulcerations with deep stromal infiltrate causing an anterior chamber cell reaction. Small, peripheral lesions are usually resolved, and patients recover a high visual acuity. Severe infections causing VA of 20/200 or worse are common and often do not significantly improve even after treatment. Vancomycin is considered the most potent antibiotic against CAK, although other antibiotics such as moxifloxacin and ceftazidime are more commonly used as first-line treatment.
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