Elsevier

Burns

Volume 33, Issue 4, June 2007, Pages 511-517
Burns

A bio-mathematical model of time prediction in corneal angiogenesis after alkali burn

https://doi.org/10.1016/j.burns.2006.08.029Get rights and content

Abstract

Background

The determination of angiogenesis time is the key prerequisite to obtaining a balance between valid repair and excessive angiogenesis in wound healing. The aim of the investigation was to establish a bio-mathematical model predicting corneal angiogenesis time after alkali burn by back propagation neural network (BP neural network).

Methods

The corneas of mice in 24 groups were burned by 0.01 mol/l NaOH. Five mice in each group were sacrificed at 6 h after alkali burn. The expression levels of vegf and tsp2, determined by real-time quantitive PCR, were used as input vectors in BP neural network. Meanwhile, the corneal angiogenesis of other mice, inspected every 3 h in 24 groups till the angiogenesis time were determined, served as output vectors. The data of 18 groups were randomly chosen for network adaptation while that of other 6 groups for simulation forecasting with functions of minmax (), postreg, prepca, trapca, respectively.

Results

A bio-mathematical model of two-level BP neural network was established, for its purpose to predict the angiogenesis time through the expression values of vegf and tsp2. The performance index (0.00999996) was smaller than the target value (0.01) after adapting 36,557 times and the accuracy rate of this predict system was 83.33%. Furthermore, the ideal regression line and the optimization regression line were almost coincident (R = 0.988 in network adaptation and R = 0.793 in simulation forecasting).

Conclusions

The investigation indicated that the bio-mathematical model had available performance of simulation and forecasting. It might provide a novel method to solve clinical problems.

Introduction

In the process of wound healing, the vascularization of cornea plays a pivotal role with its effect of double-edged sword that impacts the clinical treatment of deep corneal trauma especially in alkali burn directly. Thus, the determination of angiogenesis time is the key prerequisite to obtaining a balance between valid repair and excess angiogenesis and to different treatments before and after corneal angiogenesis.

However, the angiogenesis time of cornea is difficult to be determined by common research after trauma, for it is regulated by many factors such as injury degree, individual difference, interaction of cytokines in vivo, influence of different signal transduction pathway in vivo, surrounding irritation, repairing environment and so on [1], [2], [3]. Accordingly, it is the result of interaction between promotion and inhibition factors in vivo and the expression of single typical factor showed the effect of many factors with similar role.

As one type of artificial neural network (ANN), back propagation neural network (BP neural network) is suitable to solve this difficulty for it owned obvious superiority under some conditions as follows: the problem is not solved well by common methods, especially the problem is not known and can hardly be expressed exactly [4], [5]. Thus, the investigation adopts certain parameters as input and output vectors which reflect the typical process of corneal angiogenesis such as vegf and tsp2 in order to establish a bio-mathematical model to predict the angiogenesis time after alkali burn by BP neural network [6], [7], [8].

Section snippets

Experimental animals

Twenty-four pregnant mice were purchased from Medical Laboratory Animal Center of Institute of Surgery Research, Daping Hospital, Third Military Medical University. After spontaneous delivery, the baby mice were divided into 24 groups according to every nest with randomized female and male. Ten days after ablactating, they were used in the experiment. The investigation was approved by the research council and animal use and care committee of Daping Hospital, Third Military Medical University.

Alkali burn treatment

Corneal morphological changes and angiogenesis

Alkaline is double intermiscibility (water solubility and liposolubility) so it passes epithelium barrier easily and enters into the cells to destroy the inner cellular structure quickly and make it necrose. After treated by 0.01 mol/l NaOH, the corneas of mice mainly showed the following symptoms: epithelial lamina shrank, some tissues dissolved and alkaline substance lasted to infiltrate to the deep lamella of tissue. Meanwhile, vascular endothelial cells moved and differentiated rapidly.

Discussion

As a tissue with transparency and avascularity, cornea locates in the outside of the eyeball and will bear many kinds of injuries from ocular trauma. Some negligible injuries to other tissues may cause serious corneal consequence, especially in corneal chemical burn. The vascularization of cornea will occur when the wound depth exceeded the epithelial lamina, such as to the limbus or to the Bowman's lamina [9], [10].

Corneal angiogenesis is the result of coordination of many factors which

Acknowledgments

The work was supported by the National Key Basic Research and Development Plan of China (973 Project, 2005CB522602) and Postdoctoral Science Foundation of China (2005037165) and Natural Scientific Foundation of Chongqing (CTSC, 2004BB5251).

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