Loss of αBa-crystallin, but not αA-crystallin, increases age-related cataract in the zebrafish lens.

The vertebrate eye lens is an unusual organ in that most of its cells lack nuclei and the ability to replace aging protein. The small heat shock protein α-crystallins evolved to become key components of this lens, possibly because of their ability to prevent aggregation of aging protein that would otherwise lead to lens opacity. Most vertebrates express two α-crystallins, αA- and αB-crystallin, and mutations in each are linked to human cataract. In a mouse knockout model only the loss of αA-crystallin led to early-stage lens cataract. We have used the zebrafish as a model system to investigate the role of α-crystallins during lens development. Interestingly, while zebrafish express one lens-specific αA-crystallin gene (cryaa), they express two αB-crystallin genes, with one evolving lens specificity (cryaba) and the other retaining the broad expression of its mammalian ortholog (cryabb). In this study we used individual mutant zebrafish lines for all three α-crystallin genes to determine the impact of their loss on age-related cataract. Surprisingly, unlike mouse knockout models, we found that the loss of the αBa-crystallin gene cryaba led to an increase in lens opacity compared to cryaa null fish at 24 months of age. Loss of αA-crystallin did not increase the prevalence of cataract. We also used single cell RNA-Seq and RT-qPCR data to show a shift in the lens expression of zebrafish α-crystallins between 5 and 10 days post fertilization (dpf), with 5 and 6 dpf lenses expressing cryaa almost exclusively, and expression of cryaba and cryabb becoming more prominent after 10 dpf. These data show that cryaa is the primary α-crystallin during early lens development, while the protective role for cryaba becomes more important during lens aging. This study is the first to quantify cataract prevalence in wild-type aging zebrafish, showing that lens opacities develop in approximately 25% of fish by 18 months of age. None of the three α-crystallin mutants showed a compensatory increase in the expression of the remaining two crystallins, or in the abundant ßB1-crystallin. Overall, these findings indicate an ontogenetic shift in the functional importance of individual α-crystallins during zebrafish lens development. Our finding that the lens-specific zebrafish αBa-crystallin plays the leading role in preventing age-related cataract adds a new twist to our understanding of vertebrate lens evolution.

Improving Vertical Jump Profiles Through Prescribed Movement Plans.

Mayberry, JK, Patterson, B, and Wagner, P. Improving vertical jump profiles through prescribed movement plans. J Strength Cond Res 32(6): 1619-1626, 2018-Developing practical, reliable, and valid methods for monitoring athlete wellness and injury risk is an important goal for trainers, athletes, and coaches. Previous studies have shown that the countermovement vertical jump (CMJ) test is both a reliable and valid metric for evaluating an athlete's condition. This study examines the effectiveness of prescribed workouts on improving the quality of movement during CMJ. The data set consists of 2,425 pairs of CMJ scans for high school, college, and professional athletes training at a privately owned facility. During each scan, a force plate recorded 3 ground reaction force (GRF) measurements known to impact CMJ performance: eccentric rate of force development (ERFD), average vertical concentric force (AVCF), and concentric vertical impulse (CVI). After an initial scan, coaches either assigned the athlete a specific 1- or 2-strength movement plan (treatment group) or instructed the athlete to choose their own workouts (control group) before returning for a follow-up scan. A multivariate analysis of covariance (MANCOVA) revealed significant differences in changes to GRF measurements between athletes in the 2 groups after adjusting for the covariates sex, sport, time between scans, and rounds of workout completed. A principal component analysis of GRF measurements further identified 4 primary groups of athlete needs and the results provide recommendations for effective workout plans targeting each group. In particular, split squats increase CVI and decrease ERFD/AVCF; deadlifts increase AVCF and decrease CVI; alternating squats/split squats increase ERFD/CVI and decrease AVCF; and alternating squats/deadlifts increase ERFD/AVCF and decrease CVI.

Loss of αBa-crystallin, but not αA-crystallin, increases age-related cataract in the zebrafish lens.

The vertebrate eye lens is an unusual organ in that most of its cells lack nuclei and the ability to replace aging protein. The small heat shock protein α-crystallins evolved to become key components of this lens, possibly because of their ability to prevent aggregation of aging protein that would otherwise lead to lens opacity. Most vertebrates express two α-crystallins, αA- and αB-crystallin, and mutations in each are linked to human cataract. In a mouse knockout model only the loss of αA-crystallin led to early-stage lens cataract. We have used the zebrafish as a model system to investigate the role of α-crystallins during lens development. Interestingly, while zebrafish express one lens-specific αA-crystallin gene (cryaa), they express two αB-crystallin genes, with one evolving lens specificity (cryaba) and the other retaining the broad expression of its mammalian ortholog (cryabb). In this study we used individual mutant zebrafish lines for all three α-crystallin genes to determine the impact of their loss on age-related cataract. Surprisingly, unlike mouse knockout models, we found that the loss of the αBa-crystallin gene cryaba led to an increase in lens opacity compared to cryaa null fish at 24 months of age. Loss of αA-crystallin did not increase the prevalence of cataract. We also used single cell RNA-Seq and RT-qPCR data to show a shift in the lens expression of zebrafish α-crystallins between 5 and 10 days post fertilization (dpf), with 5 and 6 dpf lenses expressing cryaa almost exclusively, and expression of cryaba and cryabb becoming more prominent after 10 dpf. These data show that cryaa is the primary α-crystallin during early lens development, while the protective role for cryaba becomes more important during lens aging. This study is the first to quantify cataract prevalence in wild-type zebrafish, showing that lens opacities develop in approximately 25% of fish by 18 months of age. None of the three α-crystallin mutants showed a compensatory increase in the expression of the remaining two crystallins, or in the abundant ßB1-crystallin. Overall, these findings indicate an ontogenetic shift in the functional importance of individual α-crystallins during zebrafish lens development. Our finding that the lens-specific zebrafish αBa-crystallin plays the leading role in preventing age-related cataract adds a new twist to our understanding of vertebrate lens evolution.