Significance of optineurin mutations in glaucoma and other diseases.

Purpose: To evaluate the extent to which mutations in the optineurin (OPTN) glaucoma gene play a role in glaucoma in different populations. Methods: Case-controlled study of OPTN sequence variants in individuals with or without glaucoma in populations of different ancestral origins and evaluate previous OPTN reports. We analyzed 314 subjects with African, Asian, Caucasian and Hispanic ancestries included 229 cases of primary open-angle glaucoma, 51 cases of juvenile-onset open-angle glaucoma, 33 cases of normal tension glaucoma, and 371 controls. Polymerase chain reaction-amplified OPTN coding exons were resequenced and case frequencies were compared to frequencies in controls matched for ancestry. Results: The E50K sequence variant was identified in one individual from Chile with normal tension glaucoma, and the 691_692insAG variant was found in one Ashkenazi Jewish individual from Russia. The R545Q variant was found in two Asian individuals with primary open-angle glaucoma; one of Filipino ancestry and one of Korean ancestry. In addition to presenting OPTN allele frequencies for Caucasian and Asian populations that have been the subject of previous reports, we also present information for populations of Hispanic and black African ancestries. Conclusions: Our study contributes additional evidence to support the previously reported association of the OPTN E50K mutation with glaucoma. After finding an additional 691_692insAG OPTN variant, we can still only conclude that this variant is rare. Combined analysis of our data with data from more than a dozen other studies indicates no association of R545Q with glaucoma in most populations. Those same studies disagree in their conclusions regarding the role of M98K in glaucoma. Our analysis of the combined data provides statistically significant evidence of association of M98K with normal tension glaucoma in Asian populations, but not in Caucasian populations; however, the validity of this conclusion is questionable because of large differences in allele frequencies between and within populations. It is currently not possible to tell how much of the underlying cause of the allele frequency difference is attributable to demographic, technical, or ascertainment differences among the studies.

http://www-personal.umich.edu/~dmreed/Manuscripts/AyalaLugo2007.pdf

Variation in optineurin (OPTN) allele frequencies between and within populations

Optineurin (Optn) is a 577 aa protein encoded by the Optn gene. Mutations of Optn are associated with normal tension glaucoma and amyotrophic lateral sclerosis, and its gene has also been linked to the development of Paget’s disease of bone and Crohn's disease. Optn is involved in diverse cellular functions, including NF-κB regulation, membrane trafficking, exocytosis, vesicle transport, reorganisation of actin and microtubules, the cell cycle, and autophagy. Besides its role in xenophagy and autophagy of aggregates, Optn has been identified as a primary autophagy receptor, among the five adaptors that translocate to mitochondria during mitophagy. Mitophagy is a selective macroautophagy process during which irreparable mitochondria are degraded, preventing accumulation of defective mitochondria and limiting the release of reactive oxygen species and proapoptotic factors. Mitochondrial quality control via mitophagy is central to the health of cells. One of the important surveillance pathways of mitochondrial health is the recently defined signal transduction pathway involving the mitochondrial PTEN-induced putative kinase 1 (PINK1) protein and the cytosolic RING-between-RING ubiquitin ligase Parkin. Both of these proteins, when mutated, have been identified in certain forms of Parkinson’s disease. By targeting ubiquitinated mitochondria to autophagosomes through its association with autophagy-related proteins, Optn is responsible for a critical step in mitophagy. This review reports recent discoveries on the role of Optineurin in mitophagy and provides insight into its link with neurodegenerative diseases. We will also discuss the involvement of Optn in other pathologies in which mitophagy dysfunctions are involved. Specifically, we will discuss how these defects can affect metabolic reprogramming in response to stress and alter cell fate determination and differentiation, which, in turn, can lead to the loss of tissue homeostasis and development of neurodegenerative diseases and cancer.

/pdf/role-of-optineurin-in-the-mitochondrial-dysfunction-25g3cr1zco.pdf

Role of Optineurin in the Mitochondrial Dysfunction: Potential Implications in Neurodegenerative Diseases and Cancer.

Candidate genes involved in the susceptibility of primary open angle glaucoma.

Background
Glaucoma is the leading cause of irreversible blindness in the world. Recent evidence indicates a role for genetic susceptibility to primary open-angle glaucoma (POAG). The relation between myocilin polymorphisms and POAG susceptibility has been studied in different populations.

/pdf/myocilin-polymorphisms-and-primary-open-angle-glaucoma-a-2ne80v6p7n.pdf

Myocilin Polymorphisms and Primary Open-Angle Glaucoma: A Systematic Review and Meta-Analysis

OBJECTIVE: To screen the mutation loci of optic neuropathy induced response protein (OPTN) gene in Chinese with primary open-angle glaucoma (POAG) and to investigate the association between OPTN genotype and phenotype of POAG. METHODS: Specimens of peripheral blood were collected from Chinese 118 patients with POAG and 150 sex- and aged-matched subjects without POAG. Polymerase chain reaction (PCR) was used to analyze the coding sequence of OPTN gene consisting of thirteen exons. The abnormal strands by SSCP were evaluated by bi-directional sequencing. RESULTS: Eleven sequence changes were identified, 6 of which had been reported before (T34T, T49T, M98K, IVS6-SC-->T, IVS6-10G-->A, and R545Q), and 5 of which were novel (IVS6-9C-->T, IVS6-14G-->A, IVS7 + 36G-->A, IVS8-51T-->C, and K435R) Only K435R was found in patient with POAG, whereas IVS6-9C-->T and IVS6-14G-->A were present in control subjects. IVS6-5C-->T and IVS6-10G-->A showed significant association with POAG. The patients with IVS6-5C-->T sequence abnormality were aged 23 to 73 with an average intraocular pressure of 23.14 mm Hg (1 mm Hg =0. 133 kPa) and a mean defect of visual field 0.2 to 28. 2dB. The patients with IVS6-10C-->T sequence abnormality were aged 20 to 74 with an average intraocular pressure of 20.19 mm Hg and a mean defect of visual field from 0.9 to 26. 5dB. CONCLUSION: The single nucleotide polymorphism (SNP) of OPTN gene may contribute to the pathogenesis of glaucoma in Chinese.

[Study on the optic neuropathy induced response protein gene mutation in Chinese patients with primary open-angle glaucoma].

Corner detection is a common method to obtain image features, and the detection effect influences the performance of matching and tracking directly. A FAST-Harris fusion corner detection algorithm is proposed to improve the shortcomings of the Harris algorithm, such as the low detection accuracy and low positioning accuracy, and a corner detection fusion model is established. First, the detected target image is padded, and then the FAST algorithm is used with a 25% reduced contrast points to achieve fast capture roughly; in this way, a candidate corner set is obtained. Then, screening the candidate corner is set one by one by calculating the response function of the Harris with Scharr operator to achieve capture accurately. Finally, the real corners are obtained using SAD for nonmaximum suppression. The positioning error, error detection rate, robustness, and running time of corner detection are obtained by the PyCharm platform. Compared with Harris, the error detection rate and localization error of the algorithm are reduced by 16.89% and 42.04%, respectively. Compared with 8 popular corner detection algorithms, the error detection rate and localization error of the algorithm in this paper are the lowest, which are 24.60% and 1.42 pixels. The robust performance in lossy JPEG compression is the best, with 17.37% shorter running time than Harris algorithm. The method in this paper can be used in scenarios such as autonomous driving and image search services.

/pdf/a-target-corner-detection-algorithm-based-on-the-fusion-of-2c6yiqik.pdf

A Target Corner Detection Algorithm Based on the Fusion of FAST and Harris

Objective To study the mutations in the trabecular meshwork induced- glucocorticoid response protein gene (TIGR/MYOC) in Chinese POAG patients. Methods It was a case-control study.One hundred and eighteen Chinese patients with POAG and 150 control subjects without POAG were screened for coding sequence of the MYOC gene by polymerase chain reaction, single-strand conformation polymorphism (SSCP) and DNA sequence. Restriction endonuclease analysis was used to detect the SSCP in 150 gender- and aged-matched controls. Statistical significance of the difference in frequencies of MYOC mutations between POAG patients and the controls was determined by the chi-squared test. Results Three coding sequence variants that lead to amino acid changes were identified in MYOC gene. One mutation of MYOC gene was novel, I288M, which was present in one patient with POAG and 3 control subjects. G12R and Y353I have been reported previously. I288M and Y353I were found in both the subjects with and without POAG, the difference of the frequency of these two mutations between POAG and the controls was x2 =0. 07, P =0. 791 and x2 = O. 56, P = 0. 453, respectively. Coding sequence mutations of MYOC were found in 4. 23％ POAG patients. Frequency of G12R mutation in POAG patients was significantly greater than that in the controls (x2 = 4. 37, P = 0. 037). Conclusions One novel variant locus in the MYOC/TIGR (I288M) was found in the present study, but this mutation is not associated with POAG. G12R is the most common mutation in MYOC locus in Chinese subjects with POAG. Approximately 4. 23％ sporadic POAG patients have mutation in the exon 1 in MYOC/TIGR.

Key words: 
Glaucoma, open-angle ;  DNA mutational analysis;  Cytoskeletal proteins ;  Eye proteins ;  Polymorphism,single nucleotide

[Study on MYOC/TIGR gene mutations in primary open-angle glaucoma].

Objective To describe the clinical features of blepharochalasis and the effect of surgical treatment of associated deformities.Methods A retrospective study reviewed 54 patients ( 98 eyes ) with blepharochalasis.The main features analyzed included sex,age of onset,duration and clinical signs.Surgical treatment for the correction of deformities includes blepharoplasty; resuspension of the prolapsed lacrimal gland,ptosis repair,surgical correction of lower eyelid retraction and lateral canthoplasty. Followup ranged from 6 to 60 months. Results The average age of onset was 9.3 years. The duration in all 54 patients (32 females and 22 males ) lasted for 2 - 16 years and different periorbital deformities were presented.After surgical repair,all patients were satisfied with their bilateral symmetrical creases in upper eyelids and the contour of upper eyelids.The appearance of floppy eyelids has been improved distinctly.The lateral canthus moved to the normal position. No patients complained epiphora or dry eye symptoms.Prolapse of the lacrimal gland recurred in two patients ( three eyes).They underwent reoperation with no further recurrence.Overcorrection in blepharoptosis surgery of five patients was fixed with suture adjustment of the levator aponeurosis. Conclusions Blepharochalasis onset often occurs around age 10 years and stabilizes till adolescence.Since it involves bilateral or unilateral,local eye tissues or periorbital tissues,elinical manifestations may vary in blepharochalasis. Ophthalmic plastic surgery to correct blepharochalasis and its associated deformities in the quiescent stage is usually safe and with satisfactory cosmetic effects.

Key words: 
Blepharoptosis ;  Congenital abnormalities ;  Surgery, plastic

Clinical features of blepharochalasis and surgical treatment of associated deformities

Aiming at the low matching accuracy and poor robustness in video sequence image matching, a video sequence image matching algorithm based on Adaptive Gamma Correction is proposed in the paper. Firstly, Adaptive Gamma Correction is used to enhance the contrast of video sequence images. Then feature extraction and description are realized by the ORB algorithm. The RANSAC algorithm is optimized in matching by improving the interior point ratio after Brute Force Match. The experimental results show that the algorithm proposed improves the correct matching rate by 19.51%, 12.53%, and 4.87% respectively compared with the SIFT, ORB, and ORB+RANSAC algorithms without increasing the running time. Meanwhile, the algorithm in this paper has good robustness in video sequence image matching.

Yang Li

Papers

[Study on the optic neuropathy induced response protein gene mutation in Chinese patients with primary open-angle glaucoma].

A Target Corner Detection Algorithm Based on the Fusion of FAST and Harris

[Study on MYOC/TIGR gene mutations in primary open-angle glaucoma].

Clinical features of blepharochalasis and surgical treatment of associated deformities

Video Sequence Image Matching Algorithm Based on Adaptive Gamma Correction