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Background: Olfactory dysfunction is among the earliest non-motor symptoms of Parkinson's disease (PD). As the foremost pathological hallmark, α-synuclein initiates the pathology in the olfactory pathway at the early stage of PD, particularly in the olfactory epithelium (OE) and olfactory bulb (OB). However, the local neural microcircuit mechanisms underlying olfactory dysfunction between OE and OB in early PD remain unknown. Results: We observed that odor detection and discrimination were impaired in 6-month-old SNCA-A53T mice, while their motor ability remained unaffected. It was confirmed that α-synuclein increased and accumulated in OB but not in OE. Notably, the hyperactivity of mitral/tufted cells and the excitation/inhibition imbalance in OB were found in 6-month-old SNCA-A53T mice, which was attributed to the impaired GABAergic transmission and aberrant expression of GABA transporter 1 and vesicular GABA transporter in OB. We further showed that tiagabine, a potent and selective GABA reuptake inhibitor, could reverse the impaired olfactory function and GABAergic signaling in OB of SNCA-A53T mice. Conclusions: Taken together, our findings demonstrate potential synaptic mechanisms of local neural microcircuit underlying olfactory dysfunction at the early stage of PD. These results highlight the critical role of aberrant GABAergic signaling of OB in early diagnosis and provide a potential therapeutic strategy for early-stage PD. [ABSTRACT FROM AUTHOR]

Introduction: This is a cross-sectional cohort study focused on assessing the influence of ocular biometric parameters of different camera devices for accurately predicting the intraocular lens (IOL) power in congenital ectopia lentis (EL) patients. Methods: This study includes a total of 91 eyes of 60 patients with congenital EL from June 2018 to April 2021. All patients underwent lens subluxation surgery with Cionni modified capsular tension rings implantation. Ocular parameters measured by partial coherence interferometry (IOLMaster 700; Carl Zeiss Meditec AG, Jena, Germany) and rotating Scheimpflug camera (Pentacam HR system; Oculus Optikgeräte GmbH, Wetzlar, Germany) were acquired from the database. The authenticity of the different keratometries (Ks) was analyzed by comparing the prediction error in spherical equivalent under controlled formula SRK/T, Haigis, and after Wang-Koch (WK) adjustment. Results: We observed significant greater K values were obtained in IOLMaster than Pentacam, resulting in more significant hyperopia error while calculating SRK/T. The IOL power calculated with the total corneal refractive power (TCRP) from Pentacam revealed the highest prediction accuracy, indicating that TCRP is the closest to the actual refractive power of the cornea. However, in an exceptional case for long eye patients, total K from IOLMaster was better recommended when using formula Haigis with WK adjustment. Conclusions: For most instances, TCRP is the best-recommended source of K value while calculating IOL power for EL patients. However, the total K from IOLMaster preferably fits for long eye patients, who require WK adjustment for Haigis formula. [ABSTRACT FROM AUTHOR]

Mutations of fibrillin‐1 (FBN1) have been associated with Marfan syndrome and pleiotropic connective tissue disorders, collectively termed as "type I fibrillinopathy". However, few genotype–phenotype correlations are known in the ocular system. Patients with congenital ectopia lentis (EL) received panel‐based next‐generation sequencing, complemented with multiplex ligation‐dependent probe amplification. In a total of 125 probands, the ocular phenotypes were compared for different types of FBN1 mutations. Premature termination codons were associated with less severe EL and a thinner central corneal thickness (CCT) than the inframe mutations. The eyes of patients with mutations in the C‐terminal region had a higher incidence of posterior staphyloma than those in the middle and N‐terminal regions. Mutations in the TGF‐β‐regulating sequence had larger horizontal corneal diameters (white‐to‐white [WTW]), higher incidence of posterior staphyloma, but less severe EL than those with mutations in other regions. Mutations in the neonatal region were associated with thinner CCT. Longer axial length (AL) was associated with mutations in the C‐terminal region or TGF‐β regulating sequence after adjusting for age, EL severity, and corneal curvature radius. FBN1 genotype–phenotype correlations were established for some ocular features, including EL severity, AL, WTW, CCT, and so forth, providing novel perspectives and directions for further mechanistic studies. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the relationship between visual prognosis and genotype in patients undergoing lens surgery for congenital ectopia lentis (EL)., Design: Prospective clinical cohort study., Methods: Patients with congenital EL who underwent lens removal and intraocular lens implantation received panel-based next-generation sequencing. Patients were grouped into children and adolescents/adults based on the age at surgery. The visual prognosis, including best-corrected visual acuity (BCVA) and amblyopia, was stratified into short-term and medium to long-term., Results: This study included 329 probands with congenital EL, with a median age at lens surgery of 7.00 years (interquartile range [IQR] = 5.00, 12.50 years). Children with the non-FBN1 mutation exhibited inferior medium to long-term postoperative BCVA [0.26 (IQR: 0.14, 0.33) vs. 0.15 (IQR: 0.10, 0.22), P = 0.034] and a higher prevalence of amblyopia (44.4% vs. 16.8%, P = 0.012) compared to those with FBN1 mutation. Multivariable analysis showed that genotype (FBN1 vs. non-FBN1 mutation) was significantly associated with medium to long-term postoperative BCVA (b = -0.128, 95% CI -0.214 to -0.042, P = 0.004) and amblyopia (OR = 0.20, 95% CI 0.05 to 0.78, P = 0.020) in children. Further classification of FBN1 genotype did not yield significant correlations with visual prognosis. However, no significant correlation was observed between genotype and short-term visual prognosis in the children. Children with less severe EL (OR = 0.13, 95% CI 0.02 to 0.85, P = 0.033) had lower risks of amblyopia in the short-term follow-up. For adolescent and adult patients with congenital EL, those with poor preoperative BCVA and long axial length should be informed of suboptimal visual prognosis., Conclusions: Genotype significantly influences the medium to long-term visual prognosis in children with congenital EL. Genotype, along with pre-operative BCVA, may assist in establishing reasonable expectations for patients regarding their visual outcomes after the lens surgery., Competing Interests: Declaration of competing interest We declare that we do not have any commercial or associative interest that represents a conflict of interest in connection with the work submitted., (Copyright © 2024. Published by Elsevier Inc.)