ABSTRACT
Retinal ganglion cells (RGCs), the sole output neurons in the eyes, are vulnerable to diverse insults in many pathological conditions, which can lead to permanent vision dysfunction. However, the molecular and cellular mechanisms that contribute to protecting RGCs and their axons from injuries are not completely known. Here, we identify that Porf-2, a member of the Rho GTPase activating protein gene group, is upregulated in RGCs after optic nerve crush. Knockdown of Porf-2 protects RGCs from apoptosis and promotes long-distance optic nerve regeneration after crush injury in both young and aged mice in vivo. In vitro, we find that inhibition of Porf-2 induces axon growth and growth cone formation in retinal explants. Inhibition of Porf-2 provides long-term and post-injury protection to RGCs and eventually promotes the recovery of visual function after crush injury in mice. These findings reveal a neuroprotective impact of the inhibition of Porf-2 on RGC survival and axon regeneration after optic nerve injury, providing a potential therapeutic strategy for vision restoration in patients with traumatic optic neuropathy.
Subject(s)
Crush Injuries , Optic Nerve Injuries , Peripheral Nerve Injuries , Animals , Mice , Optic Nerve Injuries/genetics , Axons , Nerve Regeneration , Retina , Optic Nerve , Retinal Ganglion Cells , Crush Injuries/geneticsABSTRACT
Retinal ganglion cells (RGCs) are the sole output neurons that carry visual information from the eye to the brain. Due to various retinal and optic nerve diseases, RGC somas and axons are vulnerable to damage and lose their regenerative capacity. A basic question is whether the manipulation of a key regulator of RGC survival can protect RGCs from retinal and optic nerve diseases. Here, we found that Maf1, a general transcriptional regulator, was upregulated in RGCs from embryonic stage to adulthood. We determined that the knockdown of Maf1 promoted the survival of RGCs and their axon regeneration through altering the activity of the PTEN/mTOR pathway, which could be blocked by rapamycin. We further observed that the inhibition of Maf1 prevented the retinal ganglion cell complex from thinning after optic nerve crush. These findings reveal a neuroprotective effect of knocking down Maf1 on RGC survival after injury and provide a potential therapeutic strategy for traumatic optic neuropathy.
Subject(s)
Axons/physiology , Nerve Regeneration/physiology , Optic Nerve Injuries/genetics , Repressor Proteins/antagonists & inhibitors , Repressor Proteins/genetics , Retinal Ganglion Cells/physiology , Animals , Cell Survival/physiology , Gene Knockdown Techniques/methods , Intravitreal Injections , Mice , Mice, Inbred C57BL , Optic Nerve Injuries/metabolism , Optic Nerve Injuries/pathology , Repressor Proteins/biosynthesisABSTRACT
Object:To find out college students' perceptions about counseling.Methods:By using a questionnaire about college students' view of counseling,875 college students of Zhejiang University from grade 1 to grade 4 were tested.Results:Most students acknowledged that counseling deals with mental issues and disorders. They were willing to help clients,and prefer counselors who are like their friends and family members.They agreed that counseling is helpful and,prefer one-hour sessions,which are free of charge.