Koontz Lab

Research

Research Overview

How upstream tissue injury from prostate radiation causes erectile dysfunction

Common belief is that erectile dysfunction from radiation is caused by vascular damage in the region of the penile bulb.The cavernous nerve, which runs in the neurovascular bundle along the posterolateral surface of the prostate, has been believed to be radioresistant. However, in our work we have discovered significant morphological and functional changes in the cavernous nerve that directly correlate with the development of ED. Current research seeks to further delineate the nerve substructures that show radiation injury and the molecular pathways by which that injury occurs. We are also investigating the response of the internal pudendal artery, which feeds the penile bulb, to prostate radiotherapy.

Behavioral and pharmacological interventions to prevent radiation-induced ED

Radiation-induced normal tissue injury is generally known to be related to indirect DNA damage caused by oxidative stress and the microenvironmental response to free radical formation from ionizing radiation. This process appears to be the primary mechanism of injury in radiation-induced ED as well. Therefore antioxidant therapy may be beneficial to prevent radiation-induced impotence. Other therapies such as pathway inhibitors and exercise, are being investigated for their potential to prevent the inflammatory cascade that results in apoptosis and fibrosis in irradiated and downstream tissues.
 

Current Projects

Ability of a Novel Antioxidant to Protect Erectile Function during Prostate Radiation

This project will allow application of a fourth generation manganese porphyrin with strong superoxide dismutase properties which has been radioprotective of brain and parotid in mice to the issue of radiation-induced ED. The project will fund initial pharmacokinetics and initial experiments testing efficacy of the antioxidant to maintain erectile function after prostate radiotherapy in the rat.

  • Supported by Josiah Charles Trent Memorial Foundation

The Effect of Aerobic Exercise Training on Radiation-Induced Erectile Dysfunction in a Rodent Model of Prostate Radiotherapy

This project evaluates the use of exercise as a strategy to prevent erectile dysfunction, based on the hypothesis that exercise stimulates systemic endothelial health. Since exercise is well known to modulate endothelial and vascular beds, we are using our rat model to evaluate how exercise changes systemic endothelial stem cell production and penile endothelial recovery after prostate radiation.

  • Supported by RTOG CCOP Seed Grant

Characterization of Radiation-Induced Erectile Dysfunction in a Rat Model

This ongoing project developed the stereotactic radiation technique and dose/time relationship for development of radiation-induced ED. Current work explores the mechanisms which result in ED development.