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Sphingosine Kinase 2 Phosphorylation of FTY720 is Unnecessary for Prevention of Light-Induced Retinal Damage

Hui Qi1, Jerome Cole2, Richard C Grambergs2

  • 1Department of Ophthalmology, University of Oklahoma Health Sciences Center (OUHSC), Oklahoma City, OK, 73104, USA.

Scientific Reports
|May 25, 2019
PubMed

Insights

FTY720 protects photoreceptor cells from damage, independent of its active form FTY720-P. This finding reveals a novel mechanism for neuroprotection in the retina, highlighting FTY720

Area of Science:

  • Ophthalmology
  • Neuroscience
  • Biochemistry

Background:

  • Sphingosine kinase 2 (Sphk2) phosphorylates FTY720 to its active form, FTY720-P.
  • FTY720 treatment protects murine retinas from photoreceptor cell death.
  • The precise role of FTY720 and FTY720-P in photoreceptor protection remains unclear.

Purpose of the Study:

  • To investigate the role of Sphingosine kinase 2 (Sphk2) in FTY720-mediated retinal protection.
  • To determine if FTY720 phosphorylation is necessary for its protective effects against light-induced photoreceptor damage.

Main Methods:

  • Utilized Sphingosine kinase 2 knockout (Sphk2 KO) mice.
  • Assessed retinal sensitivity to light-induced damage in Sphk2 KO and wild-type mice.
  • Administered systemic FTY720 treatment to evaluate protection in Sphk2 KO retinas.

Main Results:

  • Sphk2 KO retinas exhibited similar light damage sensitivity compared to wild-type retinas.
  • Systemic FTY720 treatment provided significant protection to Sphk2 KO retinas.
  • FTY720 phosphorylation was markedly reduced in Sphk2 KO mice, yet protection was still observed.

Conclusions:

  • FTY720 plays an active role in preventing photoreceptor cell death.
  • The phosphorylation of FTY720 is not essential for its neuroprotective effects in the retina.

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