The hypoxia response is a fundamental phenomenon mainly regulated by hypoxia-inducible factors (HIFs). For more than a decade, we have investigated and revealed the roles of the hypoxia response in the development, physiology, and pathophysiology of the retina by generating and utilizing cell-type-specific conditional knockout mice. To investigate the functions of genes related to the hypoxia response in cells composing the retina, we generated various mouse lines that lack HIFs and/or related genes specifically in retinal neurons, astrocytes, myeloid cells, or retinal pigment epithelium cells. We found that these genes in the different types of retinal cells contribute in various ways to the homeostasis of ocular vascular and visual function. We hypothesized that the activation of HIFs is likely involved in the development and progress of retinal diseases, and we subsequently confirmed the pathological roles of HIFs in animal models of neovascular and atrophic ocular diseases. Currently, anti-vascular endothelial growth factor (anti-VEGF) therapy is a first-line treatment widely used for neovascular retinal diseases. However, alternative or additional targets are now required because several recent large-scale clinical trials and animal studies, including our own research, have indicated that VEGF antagonism may induce retinal vascular and neuronal degeneration. We have identified and confirmed a microRNA as a candidate for an alternative target against neovascular retinal diseases, and we are now working to establish a novel HIF inhibitor for clinical use based on the disease mechanism that we identified.
The suprapatellar approach for intramedullary tibial nailing has become widely accepted over the past decade. A round sleeve is passed beneath the patella to protect the surface of the patellofemoral joint (PFJ). However, the round sleeve cannot be easily stabilized in the PFJ because it does not conform to the shape of the patellar apex. Consequently, we produced a heart-shaped sleeve to simplify the insertion of the entry sleeve during the suprapatellar approach. Using the new sleeve, the following procedure is used: (1) make a longitudinal 4 cm skin incision proximal to the patella to reach the PFJ, (2) insert the guide pin manually to the ventral edge of the tibial plateau, (3) insert the cannulated trocar along the guide pin, (4) insert the heart-shaped sleeve along the cannulated trocar, (5) remove the cannulated trocar, (6) ream the entry point through the heart-shaped sleeve. Then, continue insertion of the nail in the standard manner. Among 44 patients (29 men, mean age 45.6 years, range 26–87 years) with tibial fractures treated between 2010 and 2015, the first 18 consecutive cases were performed using a round sleeve and the rest were performed using the heart-shaped sleeve. The surgery time until entry reaming commenced was 8.9 min (range 6–12 min) using the round sleeve and 6.2 min (range 3–12 min) using the heart-shaped sleeve (P < 0.05). The heart-shaped sleeve is easily stabilized in the PFJ and greatly simplifies the intramedullary nailing of tibial shaft fractures using the suprapatellar approach.