Nayak G, Odaka Y, Prasad V, Solano AF, Yeo EJ, Vemaraju S, Molkentin JD, Trumpp A, Williams B, Rao S, Lang RA. Developmental vascular regression is regulated by a wnt/β-catenin, myc and cdkn1a pathway that controls cell proliferation and cell death. Development (Cambridge). 2018; 145(12):dev154898-dev154898.
Normal development of the eye requires closely regulated development of the blood supply. Early in embryonic development, the blood supply for the retina comes from a structure called the hyaloid vasculature positioned between the lens and retina. Since this location could limit high-acuity vision, mechanisms have evolved for vessel regression. In this study, the Lang lab has shown that two regulators of cell cycle progression and cell death, CDKN1A and MYC, regulate hyaloid vessel regression and function downstream of the Wnt signaling pathway. These findings are useful new knowledge but also provide clues to mechanisms involved in vascular diseases including the pediatric condition, retinopathy of prematurity.
Goda T, Doi M, Umezaki Y, Murai I, Shimatani H, Chu ML, Nguyen VH, Okamura H, Hamada FN. Calcitonin receptors are ancient modulators for rhythms of preferential temperature in insects and body temperature in mammals. Genes and Development. 2018; 32(2):140-155.
In humans, body temperature increases during wakefulness and decreases during sleep. This circadian rhythm of body temperature is fundamentally important in the regulation of rhythmic metabolism and sleep. However, the mechanisms by which body temperature oscillates rhythmically was an unsolved mystery. Here, we show that the mediation of circadian rhythm of body temperature is surprisingly by the same family of receptors in both flies and mice: diuretic hormone 31 receptor (DH31R) in flies and calcitonin receptor (Calcr) in mice. While mammals regulate body temperature internally, ectothermic drosophila regulate body temperature by selecting an ideal temperature. This study, led by Dr. Fumika Hamada, PhD, is the first to identify the calcitonin receptor as a fundamental “ancient” mediator for circadian rhythm of body temperature.
Motley WW, Atoum D. Animal Model for Retinopathy of Prematurity Laser Surgery Training. Journal of pediatric ophthalmology and strabismus. 2017; 54:e47-e49.
A previous survey study by one of the authors, Dr. William Motley, MD, reported that half of all pediatric ophthalmology fellows believed that they received inadequate training in retinal laser photocoagulation surgery for retinopathy of prematurity (ROP), a potentially sight threatening condition in premature infants, and that instruction using an animal model would be helpful. The current study, led by Dr. Motley, shows that performing retinal laser photocoagulation surgery on the adult Dutch-Belted rabbit approximated the experience of performing the same on a human infant. The cost was economical at less than $100 per eye treated. Five Cincinnati Children's Hospital Medical Center faculty ophthalmologists also performed the procedure using the rabbit model. All of them, by anonymous survey, reported that this animal training model would provide trainees with useful experience before performing retinal laser photocoagulation surgery on human infants. These findings suggest that an inexpensive animal training model implementation can help trainees develop the skills and confidence necessary in performing laser treatment for ROP.
Rice ML, Wong B, Horn PS, Yang MB. Cataract development associated with long-term glucocorticoid therapy in Duchenne muscular dystrophy patients. Journal of American Association for Pediatric Ophthalmology and Strabismus. 2018; 22(3):192-196.
Glucocorticoid (GC) treatment is the standard of care for patients with Duchenne muscular dystrophy (DMD) and shows how to slow the decline of disease progression and stabilize muscle strength. GC treatment can have significant ocular complications, including cataract formation and increase intraocular pressure (IOP). This study, led by Dr. Melissa L Rice, OD, and Dr. Michael B Yang, MD, examined the prevalence and rate of development of cataracts in over 500 DMD patients on long-term GC treatment and also determined in a subset of patients whether there was an elevation of IOP. They found the odds of cataract development was higher for patients on deflazacort compared with prednisone. Only a small number of patients (all treated with deflazacort) developed visually significant cataracts that require cataract surgery, and only one patient had elevated IOP. This study is important because it includes the largest cohort of DMD patients evaluated to date for cataract development and increased IOP as a consequence of GC treatment, and its findings support the current protocol of annual eye evaluation for these patients.
Dosunmu EO, Hatt SR, Leske DA, Hodge DO, Holmes JM. Incidence and Etiology of Presumed Fourth Cranial Nerve Palsy: A Population-based Study. American Journal of Ophthalmology. 2018; 185:110-114.
Fourth cranial nerve palsy leads to strabismus, and it often times results in diplopia (double vision). The resulting diplopia can have significant impact on the quality of life of the affected person, and persons often adopt a head tilt/altered head position to negate the diplopia. Previous studies have evaluated the incidence and etiology of other cranial nerves that result in strabismus, and some have led to algorithms that help dictate the management of the resultant strabismus. The present study, authored by Dr. Eniolami Dosunmu, MD, was population based, and it evaluated the incidence and etiology of fourth cranial nerve palsy over a 15-year period. We found that a congenital fourth cranial nerve palsy that decompensates over time (presenting throughout adulthood) was the most common etiology (49%), followed by trauma (18%) and hypertension (18%). The authors also found that no case of isolated fourth cranial nerve palsy was the presenting sign of an intracranial tumor, which is an important finding with significant clinical implications.