2. Academic Validation
  3. Deletion of the Pedf gene leads to inflammation, photoreceptor loss and vascular disturbances in the retina

Deletion of the Pedf gene leads to inflammation, photoreceptor loss and vascular disturbances in the retina

  • Exp Eye Res. 2022 Sep;222:109171. doi: 10.1016/j.exer.2022.109171.
Xin Chen 1,  Manhong Xu 1,  Xiaomin Zhang 2,  Colin J Barnstable 3,  Xiaorong Li 4,  Joyce Tombran-Tink 5
Affiliations

Affiliations

  • 1 Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, 300384, China.
  • 2 Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, 300384, China. Electronic address: xiaomzh@126.com.
  • 3 Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, 300384, China; Department of Neural and Behavioral Sciences, Penn State College of Medicine, Hershey, PA, 17033-0850, USA.
  • 4 Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, 300384, China. Electronic address: xiaorli@163.com.
  • 5 Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, 300384, China; Department of Neural and Behavioral Sciences, Penn State College of Medicine, Hershey, PA, 17033-0850, USA. Electronic address: jttink@aol.com.
PMID: 35809620 DOI: 10.1016/j.exer.2022.109171
Abstract

Retinal diseases are often accompanied by inflammation, vascular abnormalities, and neurodegeneration that decrease vision. Treatment with exogenous PEDF is widely shown to alleviate these conditions leading us to hypothesize that loss of function of the PEDF gene disrupts these pathways and leads to visual loss. Measurements were carried out by detailed phenotyping of PEDF null mice to assess expression of immunomodulators, glia activation, systemic inflammation, vascular disturbances, and visual sensitivity often associated with retinal pathologies. With a deletion of the Pedf gene, there was increased expression of several immune modulators in Pedf-/- retinas and serum with IL-2 and GM-CSF upregulated in both. Increases in retina glia activation and macrophage infiltration, levels of serum c-reactive protein (CRP), numbers of white and red blood cells and platelets and decreased blood glucose levels were all features associated with PEDF null mice. With PEDF gene deletion, there was also a notable increase in Apoptosis in early developing retinas (PN3), reduced thickness of the photoreceptor layer, swelling of the inner plexiform layer, reduced retinal sensitivity and steady-state reduced activation of ERK and Akt, two signaling pathways used by PEDF. There is a substantial body of animal data emphasizing utility of PEDF treatment in homeostatic regulation of retinal diseases, including diabetic retinopathy and age-related macular degeneration but there is little agreement or evidence on the role of endogenous PEDF in retinal diseases. Our findings strongly support the concept that a deletion of the PEDF gene makes the retina vulnerable to diseases, and argue that endogenous PEDF plays a critical role in limiting pathological events in the retina.

Keywords

Apoptosis; Glia activation; Inflammation; Pedf(−/−); Vascular leakage.

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