氧诱导和代谢性酸中毒诱导性视网膜病变中新生血管形成的发生率和严重程度取决于大鼠来源。

Kitzmann Anna, Leske David, Chen Yi, Kendall Andrea, Lanier William, Holmes Jonathan

Mayo Medical School, Rochester, MN 55905, USA.

Curr Eye Res. 2002 Oct;25(4):215-20. doi: 10.1076/ceyr.25.4.215.13483.

PURPOSE

We have previously described oxygen-induced retinopathy (OIR) and metabolic acidosis-induced retinopathy (MAIR) in the neonatal rat, both of which are analogous to human retinopathy of prematurity (ROP). Given that rats of identical strain from two commercial suppliers are phenotypically different, we investigated the incidence and severity of preretinal neovascularization (NV) in rats from different suppliers using the OIR and MAIR models.

METHODS

Using our established models for OIR and MAIR, 400 newborn Sprague-Dawley rats, obtained from Harlan Laboratories (HSD) and Charles River Laboratories (CRSD), were raised in 16 expanded litters of 25 (6 OIR and 10 MAIR). Beginning at day 1 of life, OIR litters (3 HSD, 3 CRSD) were exposed to 7 daily cycles of hyperoxia (80% O(2), 20.5 hours) and hypoxia (10% O(2), 0.5 hours) with a gradual return to 80% O(2) over 3 hours. OIR rats were sacrificed after 5 days of room air recovery. MAIR litters (5 HSD, 5 CRSD) were raised in room air and gavaged twice daily with NH(4)Cl (10 mM/kg body weight) from day 2 through day 4. MAIR rats were sacrificed after 3 days of recovery. For both OIR and MAIR litters, retinae from left eyes were dissected, ADPase-stained, and flatmounted. Presence and severity of NV was scored and retinal vascular areas measured by a masked observer.

RESULTS

In OIR rats, the incidence of NV was higher in CRSD rats than HSD rats (73% vs. 45%, p = 0.002). NV was more severe in CRSD rats than HSD rats (median clock hours 2 vs. 0, p = 0.0001). In MAIR rats, the incidence of NV was comparable between CRSD and HSD rats (29% vs. 34%, p = 0.53) and there was no significant difference in the severity of NV.

CONCLUSIONS

Sprague-Dawley rats obtained from two independent commercial sources differed in their incidence and severity of NV associated with OIR, but not with MAIR. Future genetic studies are warranted to investigate the differences between CRSD and HSD rats, which might yield further clues into the pathogenesis of ROP.

目的

我们之前曾描述过新生大鼠中的氧诱导性视网膜病变（OIR）和代谢性酸中毒诱导性视网膜病变（MAIR），这两种病变均类似于人类早产儿视网膜病变（ROP）。鉴于来自两家商业供应商的相同品系大鼠在表型上存在差异，我们使用OIR和MAIR模型研究了不同供应商大鼠视网膜前新生血管形成（NV）的发生率和严重程度。

方法

使用我们建立的OIR和MAIR模型，将从Harlan Laboratories（HSD）和Charles River Laboratories（CRSD）获得的400只新生Sprague-Dawley大鼠饲养在16个扩大的窝中，每个窝25只（6只用于OIR，10只用于MAIR）。从出生第1天开始，OIR组的窝（3个HSD组，3个CRSD组）每天接受7个循环的高氧（80% O₂，20.5小时）和低氧（10% O₂，0.5小时）处理，并在3小时内逐渐恢复到80% O₂。OIR大鼠在恢复室内空气5天后处死。MAIR组的窝（5个HSD组，5个CRSD组）在室内空气中饲养，从第2天到第4天每天两次灌胃氯化铵（10 mM/kg体重）。MAIR大鼠在恢复3天后处死。对于OIR组和MAIR组的窝，解剖左眼视网膜，进行ADP酶染色并制成平铺标本。由一位不知情的观察者对NV的存在和严重程度进行评分，并测量视网膜血管面积。

结果

在OIR大鼠中，CRSD大鼠的NV发生率高于HSD大鼠（73%对45%，p = 0.002）。CRSD大鼠的NV比HSD大鼠更严重（中位数时钟小时数2对0，p = 0.0001）。在MAIR大鼠中，CRSD大鼠和HSD大鼠的NV发生率相当（29%对34%，p = 0.53），且NV严重程度无显著差异。