ABSTRACT
How can cells sense their own size to coordinate biosynthesis and metabolism with their growth needs? We recently proposed a motor-dependent bidirectional transport mechanism for axon length and cell size sensing, but the nature of the motor-transported size signals remained elusive. Here, we show that motor-dependent mRNA localization regulates neuronal growth and cycling cell size. We found that the RNA-binding protein nucleolin is associated with importin ß1 mRNA in axons. Perturbation of nucleolin association with kinesins reduces its levels in axons, with a concomitant reduction in axonal importin ß1 mRNA and protein levels. Strikingly, subcellular sequestration of nucleolin or importin ß1 enhances axonal growth and causes a subcellular shift in protein synthesis. Similar findings were obtained in fibroblasts. Thus, subcellular mRNA localization regulates size and growth in both neurons and cycling cells.
Subject(s)
Cell Size , Motor Neurons/metabolism , Phosphoproteins/metabolism , RNA, Messenger/metabolism , RNA-Binding Proteins/metabolism , Animals , Axons/metabolism , Mice, Transgenic , Neurogenesis , Protein Biosynthesis/physiology , NucleolinABSTRACT
OBJECTIVES: To evaluate the visual correction and clinical performance with scleral contact lenses (CL) for the visual rehabilitation of irregular astigmatism and to report the effect of brief wearing breaks on the wearing time and success rate. METHODS: A retrospective review was performed on consecutive patients who were fitted with scleral CL because of irregular astigmatism following failure of other optical corrections. Visual acuity (VA) and wearing times were abstracted. RESULTS: The 97 consecutive identified patients (155 eyes) were divided according to the diagnosis: (1) keratoconus (105 eyes; 67.7%), (2) postpenetrating keratoplasty (PK) (28 eyes; 18.1%); (3) multiple diagnoses (22 eyes; 14.2%)-postradial keratotomy, keratoglobus, pellucid marginal degeneration, PK with aphakia, and iatrogenic ectasia. The mean follow-up was 34.9 ± 18.5 months (range, 2-71 months). There was a significant increase in best VA-scleral when compared with the previous best VA-prescleral (P<0.001). The best VA-scleral was similar in the 3 groups (P>0.5). Patients who took brief breaks every 4 to 5 continuous wearing hours had a significantly higher success rate (P<0.001) among all diagnosis groups. The success rate in wearing time in the keratoconus group was significantly higher than in the PK group (P<0.001). Twenty-six patients (27%) discontinued to wear scleral lenses. CONCLUSION: Scleral lenses can be used successfully for visual rehabilitation and management of irregular astigmatism from various causative factors. The daily wearing time was significantly improved by taking brief breaks for replenishing the CL.
