An Analysis of the Retinal Vascular Development in a Mouse Model of Bronchopulmonary Dysplasia

Abstract

 

Purpose

 

To study retinal vasculature development in an established mouse model of Bronchopulmonary Dysplasia (BPD).

 

Methods

 

A total of 24 eyes from 24 C57Bl6 mice were examined. Half the mice were exposed to 14 days of hyperoxia (75% O2) immediately following birth in order to induce BPD. The other half was reared under normoxic conditions. At day 14, the mice were sacrificed, and their eyes were fixed and subsequently flatmounted and the vasculature stained with Isolectin B4. Images of the retinal vasculature were thresholded using the NIH’s ImageJ software. The resulting vessel maps were then analyzed using the NCI’s AngioTool software to determine average vessel length, the number of vessel junctions and the lacunarity of each vessel map. The hyperoxia exposed BPD eyes were then compared to the normoxic controls using these measurements.

 

Results

 

The BPD pups exhibited severely reduced vascularization with only 30% of the average vascular area of the normoxic pups (p<.01). Average vessel length in the BPD pups was 12% of the normoxic groups (p<.01). The total number of junctions in the BPD vessels was 8.6% of normoxic controls (p<.01). Lacunarity, a measure of the average gap between the blood vessels was increased in the BPD mice was 490% higher compared to the normoxic pups (p<.01).

 

Conclusions

 

Retinal vascular development in the BPD mouse model is significantly impaired compared to control pups. Overall, the retina of BPD mice is less vascularized, less organized and coherent. The BPD model presents a challenge to retinal development both from hyperoxic exposure and decreased blood flow and oxygenation due to BPD. Further study may help elucidate the individual contribution of both challenges to retinal dysfunction that we have characterized in this study. Given the frequent concurrence of BPD and Retinopathy of Prematurity (30%), determining influence of BPD conditions on retinal vascular development may elucidate future therapeutic strategies for treating both diseases.

 

 

Image 1: Isolectin stained flatmount of a normoxic retina.

 

 

Image 2: Isolectin Stained BPD retina with avascular posterior pole and large disorganized vascular channels .

 

Keywords: 706 retinopathy of prematurity • 700 retinal neovascularization • 688 retina