Identification of novel drug targets for diabetic retinopathy: proteome-wide mendelian randomization and colocalization analyses

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Aims: To identify plasma proteins with causal links to diabetic retinopathy (DR) for potential therapeutic targets. Materials and methods: Summary statistics of plasma protein quantitative trait loci (pQTL) were derived from two extensive GWAS datasets and one systematic review, with over 100 thousand participants covering thousands of plasma proteins. DR data were sourced from the largest FinnGen study, comprising 10,413 DR cases and 30,863 European controls. Two-sample MR approach was utilized to investigate the causality of plasma proteins with DR, followed by bidirectional MR, Bayesian Co-localization analysis, and phenotype scanning to ensure robustness of the MR results. Druggability of the identified proteins were systematically evaluated. Results: Genetically predicted levels of 24 proteins were significantly associated with DR risk after multiple testing correction. For each standard deviation increase in plasm protein levels, the odds ratio (OR) for DR varied from 0.51 (95% CI: 0.36-0.73; P=2.22×10-5) for Tubulin Polymerization-Promoting Protein Family Member 3 (TPPP3) to 2.02 (95% CI: 1.44-2.83; P=5.01×10-5) for Olfactomedin like 3 (OLFML3). Four proteins exhibited strong co-localization evidence (PH4 ≥0.8): WARS, ACRBP, and ICAM1 were negatively associated with DR risk, while NOTCH2 showed a positive association. Drugability assessments highlighted these 24 proteins as potential DR targets, with two of them currently in phase I clinical trials. Conclusions: Twenty-four promising drug targets for DR were identified, including four plasma proteins with particularly promise. These findings offer new insights into DR's etiology and therapeutic targeting, exemplifying the value of genomic and proteomic data in drug target discovery.
Original Article

Changes in crystalline lens parameters during accommodation evaluated using swept source anterior segment optical coherence tomography

:44-55
 

Backgrounds: To assess changes in anterior segment biometry during accommodation using a swept source anterior segment optical coherence tomography (SS-OCT).

Methods: One hundred-forty participants were consecutively recruited in the current study. Each participant underwent SS-OCT scanning at 0 and -3 diopter (D) accommodative stress after refractive compensation, and ocular parameters including anterior chamber depth (ACD), anterior and posterior lens curvature, lens thickness (LT) and lens diameter were recorded. Anterior segment length (ASL) was defined as ACD plus LT. Lens central point (LCP) was defined as ACD plus half of the LT. The accommodative response was calculated as changes in total optical power during accommodation.

Results: Compared to non-accommodative status, ACD (2.952±0.402 vs. 2.904±0.382 mm, P<0.001), anterior (10.771±1.801 vs. 10.086±1.571 mm, P<0.001) and posterior lens curvature (5.894±0.435 vs. 5.767±0.420 mm, P<0.001), lens diameter (9.829±0.338 vs. 9.695±0.358 mm, P<0.001) and LCP (4.925±0.274 vs. 4.900±0.259 mm, P=0.010) tended to decreased and LT thickened (9.829±0.338 vs. 9.695±0.358 mm, P<0.001), while ASL (6.903±0.279 vs. 6.898±0.268 mm, P=0.568) did not change significantly during accommodation. Younger age (β=0.029, 95% CI: 0.020 to 0.038, P<0.001) and larger anterior lens curvature (β= -0.071, 95% CI: -0.138 to -0.003, P=0.040) were associated with accommodation induced greater steeping amplitude of anterior lens curvature. The optical eye power at 0 and -3 D accommodative stress was 62.486±2.284 and 63.274±2.290 D, respectively (P<0.001). Age was an independent factor of accommodative response (β= -0.027, 95% CI: -0.038 to -0.016, P<0.001).

Conclusions: During -3 D accommodative stress, the anterior and posterior lens curvature steepened, followed by thickened LT, fronted LCP and shallowed ACD. The accommodative response of -3 D stimulus is age-dependent.

Original Article

Changes in corneal curvature and aberrations after cataract surgery

:67-74
 

Background: Surgically induced astigmatism (SIA) and corneal high-order aberrations (HOAs) are the two main causes of poor visual quality after cataract surgery. Changes in the parameters of corneal HOAs after cataract surgery and their effects on and relationships with changes in corneal curvature have not yet been reported. This study aimed to explore changes in anterior, posterior and total corneal curvature, astigmatism and HOAs after microincision cataract surgery.

Methods: Sixty-one age-related cataract patients (61 eyes) were included in this prospective study. The total, anterior and posterior corneal astigmatism and corneal HOAs were analyzed by anterior segment optical coherence tomography (AS-OCT) and iTrace before, one day, one week and three months after 2.2 mm temporal microincision coaxial phacoemulsification to evaluate the changes in anterior, posterior and total corneal curvature, astigmatism and corneal HOAs.

Results: The mean J0 and J45 values of anterior, posterior and total corneal curvature obtained by AS-OCT showed no statistically significant difference between preoperatively and any postoperative follow-up. SIA occurred on the anterior, posterior and total corneal surfaces and showed no statistically significant difference at any postoperative follow-up. No significant changes in 3rd-order oblique trefoil, vertical coma or 4th-order spherical aberrations were observed after surgery except for a significant increase in horizontal coma at postoperative day 1 (POD1).

Conclusions: There were no significant changes in corneal curvature after 2.2 mm temporal microincision coaxial phacoemulsification, and the corneal HOAs were not changed significantly except for the increase in horizontal coma at POD1, which may be one of the main reasons of poor visual quality at POD1 in some cataract patients who have good uncorrected or corrected distance vision.

Original Article

Changes in crystalline lens parameters during accommodation evaluated using swept source anterior segment optical coherence tomography

:-
 

Backgrounds: To assess changes in anterior segment biometry during accommodation using a swept source anterior segment optical coherence tomography (SS-OCT).

Methods: One hundred-forty participants were consecutively recruited in the current study. Each participant underwent SS-OCT scanning at 0 and ?3 diopter (D) accommodative stress after refractive compensation, and ocular parameters including anterior chamber depth (ACD), anterior and posterior lens curvature, lens thickness (LT) and lens diameter were recorded. Anterior segment length (ASL) was defined as ACD plus LT. Lens central point (LCP) was defined as ACD plus half of the LT. The accommodative response was calculated as changes in total optical power during accommodation.

Results: Compared to non-accommodative status, ACD (2.952±0.402 vs. 2.904±0.382 mm, P<0.001), anterior (10.771±1.801 vs. 10.086±1.571 mm, P<0.001) and posterior lens curvature (5.894±0.435 vs. 5.767±0.420 mm, P<0.001), lens diameter (9.829±0.338 vs. 9.695±0.358 mm, P<0.001) and LCP (4.925±0.274 vs. 4.900±0.259 mm, P=0.010) tended to decreased and LT thickened (9.829±0.338 vs. 9.695±0.358 mm, P<0.001), while ASL (6.903±0.279 vs. 6.898±0.268 mm, P=0.568) did not change significantly during accommodation. Younger age (β=0.029, 95% CI: 0.020 to 0.038, P<0.001) and larger anterior lens curvature (β=?0.071, 95% CI: ?0.138 to ?0.003, P=0.040) were associated with accommodation induced greater steeping amplitude of anterior lens curvature. The optical eye power at 0 and ?3 D accommodative stress was 62.486±2.284 and 63.274±2.290 D, respectively (P<0.001). Age was an independent factor of accommodative response (β=?0.027, 95% CI: ?0.038 to ?0.016, P<0.001).

Conclusions: During ?3 D accommodative stress, the anterior and posterior lens curvature steepened, followed by thickened LT, fronted LCP and shallowed ACD. The accommodative response of ?3 D stimulus is age-dependent.

Original Article

Changes in crystalline lens parameters during accommodation evaluated using swept source anterior segment optical coherence tomography

:-
 
Backgrounds: To assess changes in anterior segment biometry during accommodation using a swept source anterior segment optical coherence tomography (SS-OCT). Methods: One hundred-forty participants were consecutively recruited in the current study. Each participant underwent SS-OCT scanning at 0 and -3 diopter (D) accommodative stress after refractive compensation, and ocular parameters including anterior chamber depth (ACD), anterior and posterior lens curvature, lens thickness (LT) and lens diameter were recorded. Anterior segment length (ASL) was defined as ACD plus LT. Lens central point (LCP) was defined as ACD plus half of the LT. The accommodative response was calculated as changes in total optical power during accommodation. Results: Compared to non-accommodative status, ACD (2.952±0.402 vs. 2.904±0.382 mm, P<0.001), anterior (10.771±1.801 vs. 10.086±1.571 mm, P<0.001) and posterior lens curvature (5.894±0.435 vs. 5.767±0.420 mm, P<0.001), lens diameter (9.829±0.338 vs. 9.695±0.358 mm, P<0.001) and LCP (4.925±0.274 vs. 4.900±0.259 mm, P=0.010) tended to decreased and LT thickened (9.829±0.338 vs. 9.695±0.358 mm, P<0.001), while ASL (6.903±0.279 vs. 6.898±0.268 mm, P=0.568) did not change significantly during accommodation. Younger age (β=0.029, 95% CI: 0.020 to 0.038, P<0.001) and larger anterior lens curvature (β=-0.071, 95% CI: -0.138 to -0.003, P=0.040) were associated with accommodation induced greater steeping amplitude of anterior lens curvature. The optical eye power at 0 and -3 D accommodative stress was 62.486±2.284 and 63.274±2.290 D, respectively (P<0.001). Age was an independent factor of accommodative response (β=-0.027, 95% CI: -0.038 to -0.016, P<0.001). Conclusions: During -3 D accommodative stress, the anterior and posterior lens curvature steepened, followed by thickened LT, fronted LCP and shallowed ACD. The accommodative response of -3 D stimulus is age-dependent.
Original Article

Changes in corneal curvature and aberrations after cataract surgery

:-
 

Background: Surgically induced astigmatism (SIA) and corneal high-order aberrations (HOAs) are the two main causes of poor visual quality after cataract surgery. Changes in the parameters of corneal HOAs after cataract surgery and their effects on and relationships with changes in corneal curvature have not yet been reported. This study aimed to explore changes in anterior, posterior and total corneal curvature, astigmatism and HOAs after microincision cataract surgery.

Methods: Sixty-one age-related cataract patients (61 eyes) were included in this prospective study. The total, anterior and posterior corneal astigmatism and corneal HOAs were analyzed by anterior segment optical coherence tomography (AS-OCT) and iTrace before, one day, one week and three months after 2.2 mm temporal microincision coaxial phacoemulsification to evaluate the changes in anterior, posterior and total corneal curvature, astigmatism and corneal HOAs.

Results: The mean J0 and J45 values of anterior, posterior and total corneal curvature obtained by AS-OCT showed no statistically significant difference between preoperatively and any postoperative follow-up. SIA occurred on the anterior, posterior and total corneal surfaces and showed no statistically significant difference at any postoperative follow-up. No significant changes in 3rd-order oblique trefoil, vertical coma or 4th-order spherical aberrations were observed after surgery except for a significant increase in horizontal coma at postoperative day 1 (POD1).

Conclusions: There were no significant changes in corneal curvature after 2.2 mm temporal microincision coaxial phacoemulsification, and the corneal HOAs were not changed significantly except for the increase in horizontal coma at POD1, which may be one of the main reasons of poor visual quality at POD1 in some cataract patients who have good uncorrected or corrected distance vision.

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  • 眼科学报

    主管:中华人民共和国教育部
    主办:中山大学
    承办:中山大学中山眼科中心
    主编:林浩添
    主管:中华人民共和国教育部
    主办:中山大学
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  • Eye Science

    主管:中华人民共和国教育部
    主办:中山大学
    承办:中山大学中山眼科中心
    主编:林浩添
    主管:中华人民共和国教育部
    主办:中山大学
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