Related Experiment Video

Updated: May 21, 2025

Organotypic Retinal Explant Cultures from Macaque Monkey
10:32

Organotypic Retinal Explant Cultures from Macaque Monkey

Published on: August 24, 2022

1.2K

Pten Loss Triggers Progressive Photoreceptor Degeneration in an mTORC1-Independent Manner

Joseph Hanna1,2,3, Yacine Touahri1,3,4, Alissa Pak1,2

  • 1Biological Sciences Platform, Sunnybrook Research Institute, Toronto, Ontario, Canada.

Investigative Ophthalmology & Visual Science
|March 21, 2025
PubMed
Abstract

Insights

Silencing Phosphatase and tensin homolog (Pten) in the retina causes progressive photoreceptor degeneration, challenging its use for neurological disorder treatments. mTORC1 suppression worsens this degeneration, indicating Pten-mTORC1 pathway manipulation may not be therapeutic.

Area of Science:

  • Ophthalmology
  • Neuroscience
  • Cell Biology

Background:

  • Phosphatase and tensin homolog (Pten) is a key regulator of cell signaling and metabolism.
  • Pten inhibition is explored for tissue regeneration in neurological disorders.
  • Pten influences mTORC1 and glycolysis, pathways relevant to regeneration.

Purpose of the Study:

  • To investigate the long-term effects of Pten inactivation on retinal photoreceptor survival.
  • To identify downstream signaling pathways affected by Pten loss in the retina.

Main Methods:

  • Assessed retinal integrity in Pten conditional knock-out (cKO) mouse models (RPC-specific and rod-specific).
  • Examined photoreceptor gene expression, cell survival, and glial activation.
  • Investigated the impact of mTORC1 inhibition (rapamycin) and glycolysis inhibition (2DG) on Pten-deficient retinas.

Main Results:

  • Pten loss led to early downregulation of photoreceptor genes and progressive rod and cone degeneration.
  • Inactivated Pten induced retinal inflammation, astrogliosis, microgliosis, and increased angiogenesis.
  • Subretinal amyloid-beta deposits formed in Pten RPC-cKOs.
  • Rapamycin accelerated photoreceptor degeneration, while 2DG had no significant effect.

Conclusions:

  • Pten inactivation in retinal progenitor cells or mature rod photoreceptors causes retinal degeneration.
  • The pro-regenerative role of mTORC1 is confirmed, as its suppression exacerbates Pten-loss-induced degeneration.
  • Therapeutic strategies targeting Pten and mTORC1 for retinal regeneration require careful consideration.

More Related Videos

Imaging Ca2+ Dynamics in Cone Photoreceptor Axon Terminals of the Mouse Retina09:05

Imaging Ca2+ Dynamics in Cone Photoreceptor Axon Terminals of the Mouse Retina

Published on: May 6, 2015

10.7K
Optical Coherence Tomography: Imaging Mouse Retinal Ganglion Cells In Vivo08:17

Optical Coherence Tomography: Imaging Mouse Retinal Ganglion Cells In Vivo

Published on: September 22, 2017

19.1K

Related Concept Videos

PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
3.3K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
3.7K
The Retinoblastoma Gene01:20

The Retinoblastoma Gene

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
4.0K
Photoreceptors and Visual Pathways01:22

Photoreceptors and Visual Pathways

At the molecular level, visual signals trigger transformations in photopigment molecules, resulting in changes in the photoreceptor cell's membrane potential. The photon's energy level is denoted by its wavelength, with each specific wavelength of visible light associated with a distinct color. The spectral range of visible light, classified as electromagnetic radiation, spans from 380 to 720 nm. Electromagnetic radiation wavelengths exceeding 720 nm fall under the infrared category,...
5.5K
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.4K