Biomedical subjects

J M Holmes

Publications and source records attributed to J M Holmes.

At least 19 recordsLinked to original sources

PubMed2003

Temperature-dependent developmental variation in lobster muscle myosin heavy chain isoforms.

The temperature- and developmental-regulation of myosin heavy chain (MyHC) expression and primary sequence was investigated in the abdominal musculature of developing Homarus gammarus larvae acclimated to 10, 14 and 19+/-1 degrees C. MyHC loop 1 (ATP binding) and loop 2 (actin binding) regions were sequenced and compared. The deduced amino acid sequence of MyHC loop 1 showed a development-related increase in net charge from +1 to +2 between larval stages 1 and 2, which was not temperature-dependent. In post-settled stage 9 larvae, minor shifts in amino acid sequence occurred at 19 degrees C, and corresponded to a significant up-regulation of fast myosin mRNA expression. However, no temperature-specific loop 1 isoforms were detected. The deduced amino acid sequence of MyHC loop 2 was not affected by temperature, and the net charge remained +4 throughout development. These findings contrast to previous studies using the common carp, in which temperature-specific MyHC isoform genes were expressed in response to disparate thermal regimes. This raises the question as to whether arthropods do not express specific temperature isoforms but instead rely on shifts in fibre type to accommodate alterations in thermal environment.

Amino Acid Sequence↗

PubMed2002

Comparison of the variable loop regions of myosin heavy chain genes from Antarctic and temperate isopods.

The evolutionary adaptations of functional genes to life at low temperatures are not well characterised in marine and fresh water invertebrates. Temperature has been shown to affect the functional characteristics of fish muscles, with changes in the velocity of shortening and ATPase activity being associated with myosin heavy chain (MyHC) isoform composition and the structure of the surface loop regions. Two PCR products spanning loops 1 and 2 of a MyHC gene from an Antarctic isopod (Glyptonotus antarcticus) were sequenced and compared with those of a temperate isopod (Idotea resecata), slow and fast fibres from lobster (Homarus gammarus) and a cold water amphipod (Eulimnogammarus verrucosus), revealing specific differences between the species, possibly related to fibre type and habitat temperature. The loop 2 region from G. antarcticus myosin was cloned and used for Northern analysis of total RNA from the other species. The cloned myosin cDNA hybridised specifically to a 6.6-kb transcript, in G. antarcticus muscle. In contrast, cDNA probes for lobster slow myosin and actin hybridised to muscle RNA from all species, demonstrating that a distinct MyHC isoform is expressed in the Antarctic isopod, as opposed to the temperate species. The inter- and intra-specific sequence differences in loop 2 region suggest that this may be a site for muscle adaptation to enable function at the low temperatures found in the Southern Ocean.

Actins↗

PubMed2001

The amblyopia treatment study visual acuity testing protocol.

OBJECTIVE: To evaluate the reliability of a new visual acuity testing protocol for children using isolated surrounded HOTV optotypes. METHODS: After initial pilot testing and modification, the protocol was evaluated using the Baylor-Video Acuity Tester (BVAT) to present isolated surrounded HOTV optotypes. At 6 sites, the protocol was evaluated for testability in 178 children aged 2 to 7 years and for reliability in a subset of 88 children. Twenty-eight percent of the 178 children were classified as having amblyopia. RESULTS: Using the modified protocol, testability ranged from 24% in 2-year-olds to 96% in 5- to 7-year-olds. Test-retest reliability was high (r = 0.82), with 93% of retest scores within 0.1 logMAR unit of the initial test score. The 95% confidence interval for an acuity score was calculated to be the score +/-0.125 logMAR unit. For a change between 2 acuity scores, the 95% confidence interval was the difference +/-0.18 logMAR unit. CONCLUSIONS: The visual acuity protocol had a high level of testability in 3- to 7-year-olds and excellent test-retest reliability. The protocol has been incorporated into the multicenter Amblyopia Treatment Study and has wide potential application for standardizing visual acuity testing in children.

Amblyopia↗

PubMed2001

Computerized method of visual acuity testing: adaptation of the amblyopia treatment study visual acuity testing protocol.

PURPOSE: To report a computerized method for determining visual acuity in children using the Amblyopia Treatment Study visual acuity testing protocol. METHODS: A computerized visual acuity tester was developed that uses a programmed handheld device that uses the Palm operating system (Palm, Inc, Santa Clara, California). The handheld device communicates with a personal computer running a Linux operating system and 17-inch monitor. At a test distance of 3 m, single letters can be displayed from 20/800 to 20/12. A C program on the handheld device runs the Amblyopia Treatment Study visual acuity testing protocol. Using this method, visual acuity was tested in both the right and left eyes, and then the testing was repeated in 156 children age 3 to 7 years at four clinical sites. RESULTS: Test-retest reliability was high (r =.92 and 0.95 for and right and left eyes, respectively), with 88% of right eye retests and 94% of left eye retests within 0.1 logarithm of minimal angle of resolution (logMAR) units of the initial test. The 95% confidence interval for an acuity score was calculated to be the score +/- 0.13 logMAR units. For a change between two acuity scores, the 95% confidence interval was the difference +/- 0.19 logMAR units. CONCLUSIONS: We have developed a computerized method for measurement of visual acuity. Automation of the Amblyopia Treatment Study visual acuity testing protocol is an effective method of testing visual acuity in children 3 to 7 years of age.

Amblyopia↗

PubMed2001

Photographic and clinical techniques for outcome assessment in sixth nerve palsy.

PURPOSE: There are few data on the reproducibility of clinical assessment of ductions and alignment. We evaluated photographic methods that may be used for masked outcome determination in a clinical trial and compared them with clinical measures. DESIGN: Interexaminer reliability study. PARTICIPANTS: Twenty-three patients with unilateral sixth nerve palsy and three control participants were clinically evaluated by two masked examiners. MAIN OUTCOME MEASURES: Abduction deficit was graded as 0 to -5. Simultaneous prism and cover tests (SPCT) and alternate cover tests (ACT) were performed at distance and near fixation. Photographs were taken of abduction and distance alignment by each examiner. The photographs were evaluated by a third masked reader, who assigned abduction grade, measured absolute abduction (mm) and relative abduction (%), and calculated alignment in prism diopters (pd). Agreement was evaluated by calculating intraclass correlation coefficients (r(i)), weighted kappa statistics (kappa), and Spearman rank correlation coefficients (r(S)). RESULTS: There was excellent agreement between the two clinicians in clinical abduction deficit (kappa = 0.86) SPCT and ACT at distance and near (r(i) 0.94-0.96), between the clinical grade and masked photographic grade (kappa = 0.83), and between the two sets of photographs for absolute abduction and relative abduction (r(i) = 0.98 and 0.97). Both photographic measures of abduction correlated well with the clinical grade (r(S) = -0.96 for each). Measurements of alignment from photographs correlated with clinical SPCT measurement (r(i) = 0.88), but had a lower level of absolute agreement (38% within 5 pd) than between two independent SPCT measurements (96% within 5 pd). CONCLUSIONS: The excellent interexaminer agreement of our new photographic abduction assessment and of masked clinical measures suggest that these methods would be useful in clinical trials. In contrast, our simple method of photographic assessment of alignment lacks excellent agreement with the clinical assessment. These data are important in planning clinical trials in strabismus.

Abducens Nerve Diseases↗

PubMed2001

Predictors of nonrecovery in acute traumatic sixth nerve palsy and paresis.

PURPOSE: To evaluate whether nonrecovery from acute traumatic sixth nerve palsy could be predicted from demographic factors or palsy characteristics. DESIGN: Prospective, observational case series SETTING: Multicenter (academic and private practices). OUTCOME MEASURE: Nonrecovery, defined as the presence of diplopia in primary position or more than 10 prism diopters of distance esotropia in primary position at 6 months after onset. METHODS: Using data from a previously described cohort of 84 eligible patients with acute traumatic sixth nerve palsy, we performed multivariate analyses of demographic factors and palsy characteristics. RESULTS: Nonrecovery at 6 months after onset was associated with a complete palsy (adjusted risk ratio, 9.11; 95% confidence interval [CI], 2.77-14.84) and with a bilateral palsy or paresis (adjusted risk ratio, 2.53; 95% CI, 0.98-4.29). The choice of conservative management (observation, prism, or patch) versus acute injection of Botulinum toxin (within 3 months of injury) did not influence final recovery. CONCLUSIONS: In acute traumatic sixth nerve palsy or paresis, failure to recover by 6 months after onset was associated independently with inability to abduct past midline at presentation and bilaterality. Although the overall recovery rate is high in acute traumatic sixth nerve palsy or paresis, a complete or bilateral case has a poor prognosis and is more likely to need strabismus surgery.

Abducens Nerve Diseases↗

PubMed2001

Amblyopia. Current clinical studies.

Over the next two years, results from several multi-center amblyopia treatment studies will become available. These data may have a profound influence on our approach to treating this condition. This is indeed an exciting time to be taking care of children with amblyopia, as we anticipate the results of these studies.

Amblyopia↗

PubMed2001

The Amblyopia Treatment Index.

OBJECTIVE: To develop a questionnaire to assess the acceptability of amblyopia treatment and its effect on the child and family. METHODS: A 20-item parental survey was developed and pilot tested on 64 subjects, aged 3 to 6 years, participating in the Amblyopia Treatment Study, a randomized trial comparing patching and atropine as treatments for moderate amblyopia. The survey was administered after 4 weeks of treatment. A descriptive item analysis and an internal consistency reliability analysis were performed. RESULTS: Nineteen of the 20 items demonstrated adequate variability as evidenced by the frequency distributions for item responses. Only 4 (<1%) of 1280 possible item responses were missing, one each by 4 different respondents. Factor analysis identified 3 treatment-related factors--"adverse effects," "compliance," and "social stigma"--among 11 of the 20 items. The internal-consistency reliability alpha for the 5-item adverse effects subscale was 0.82, the 4-item compliance subscale alpha was 0.81, and the 2-item social stigma subscale alpha was 0.84. CONCLUSIONS: The Amblyopia Treatment Index appears to be a useful instrument for assessing the impact of amblyopia treatment in 3- to 6-year-old children.

Amblyopia↗

PubMed2001

Initial treatment outcomes in chronic sixth nerve palsy.

INTRODUCTION: We conducted a prospective multi-center, nonrandomized, data-collection study of patients with chronic sixth cranial nerve palsy. We evaluated success rates with conservative nonsurgical management, botulinum toxin (botox) treatment, strabismus surgery, and a combination of botox treatment and surgery. METHODS: All members of the American Association for Pediatric Ophthalmology and Strabismus and the North American Neuro-Ophthalmology Society were invited to enroll patients with sixth nerve palsy or paresis of more than 6 months duration over a 2-year period (between March 1998 and February 2000). The botox and surgical groups received intervention within 3 months of enrollment. Success at 6 months from enrollment was defined as absence of diplopia in primary position and no more than 10 prism diopters (pd) distance esotropia in primary position. Patients with no follow-up were excluded. RESULTS: Fifty-six eligible patients were enrolled by 33 investigators. Eighteen (32%) were traumatic in etiology, 15 (27%) were unknown (including presumed hypertensive), 14 (25%) were neoplastic, 2 (4%) were diabetic, and 7 (13%) were other. Twenty (35%) were managed conservatively without surgery, 10 (18%) with botox treatment, 19 (33%) with surgery, and 8 (14%) with a combination of botox treatment and surgery. Success at 6 months from enrollment was 15% in the conservatively managed cases, 10% with botox alone, 39% with surgery alone, and 25% with a combination of botox and surgery. CONCLUSIONS: This study demonstrates that management of chronic sixth nerve palsy and paresis remains challenging. Spontaneous recovery occurs but is uncommon. Botox treatment alone was rarely successful, and a single surgical procedure had a lower-than-expected success rate. Care should be taken in directly comparing success rates between treatment groups because of bias in patient selection.

Abducens Nerve Diseases↗

PubMed2001

Postnatal growth retardation exacerbates acidosis-induced retinopathy in the neonatal rat.

PURPOSE: We have previously described a metabolic acidosis-induced retinopathy in the neonatal rat, similar to retinopathy of prematurity (ROP). We also have reported exacerbation of oxygen-induced retinopathy by postnatal growth retardation, produced by raising newborn rats in 'expanded' litters. In the present study, we investigated the effect of postnatal growth retardation on the incidence and severity of acidosis-induced retinopathy. METHODS: 100 newborn Sprague-Dawley rats were randomly assigned to two expanded litters of 25 pups each and five standard control litters of 10 pups each. All rats were gavaged with 10 mM/kg NH(4)Cl twice daily from days two to seven. Following five days of recovery, retinal vasculature was assessed using ADPase staining, light microscopy, and computer-assisted image analysis. The presence of neovascularization (NV), severity of NV (clock hours), and vascularized retinal areas, were evaluated in a masked manner. RESULTS: NV occurred in 52% of rats in expanded litters versus 18% of rats in standard control litters (p = 0.005). Postnatal growth retardation of pups in expanded litters was confirmed by comparing total body weight of pups raised in expanded and standard control litters (10.8g vs 13.4g on day 8, p < 0.001; 20.8g vs 25.2g on day 13, p = 0.002). CONCLUSIONS: Postnatal growth retardation increases the incidence of acidosis-induced retinopathy in the neonatal rat. Our study provides further evidence that postnatal growth retardation is a risk factor for preretinal neovascularization in immature retinae and is consistent with the clinical observation that the smallest and sickest premature infants are more likely to suffer from ROP.

Acidosis↗

PubMed2001

Age-appropriate HIV prevention messages for older adults: findings from focus groups in New York State.

The Emerging Issues Committee of the New York State HIV Prevention Planning Group identified that prevention messages were not including persons 50 and older and that 15 percent of the newly reported AIDS cases in 1997 in New York were in this age group. Recognizing that there may be unique needs in targeting prevention messages for this age group, a consultant conducted five focus groups throughout the state to speak with people to determine what they identified as unique themes related to HIV prevention for this age group.

Aged↗

PubMed2001

Preretinal neovascularization associated with acetazolamide-induced systemic acidosis in the neonatal rat.

PURPOSE: NH4Cl gavage in the neonatal rat produces a metabolic acidosis-induced retinopathy which serves as a model for retinopathy of prematurity (ROP). Acetazolamide induces a metabolic acidosis via an alternative biochemical mechanism (bicarbonate loss versus hydrogen ion load). In the present study, the following hypothesis was tested: acetazolamide-induced acidosis is associated with preretinal neovascularization in the neonatal rat. METHODS: All studies used newborn Sprague-Dawley rats raised in expanded litters of 25. Arterial blood pH was measured to determine the level of acidosis induced by intraperitoneal (IP) acetazolamide (50 or 200 mg/kg) or saline. In a separate retinopathy study, newborn rats (n = 75) were randomized to either IP acetazolamide, 50 mg/kg (low-dose), or IP saline twice daily from days 2 to 7. After 5 days of recovery, retinal vasculature was assessed using ADPase staining and light microscopy. The presence and severity (clock hours) of neovascularization were assessed by three masked observers. In an additional retinopathy study, newborn rats (n = 100) were randomized to either IP acetazolamide, 200 mg/kg (high-dose), or IP saline twice daily from days 2 to 7. After 5 days of recovery, the retinas were similarly analyzed. RESULTS: Neovascularization occurred in 59% of rats receiving high-dose acetazolamide (200 mg/kg). High-dose acetazolamide produced a severe acidosis (pH 7.13 +/- 0.06) during drug delivery. Low-dose acetazolamide (50 mg/kg) produced a pH (7.22 +/- 0.07) that was intermediate between high-dose (200 mg/kg) acetazolamide (P < 0.001) and saline controls (7.42 +/- 0.06, P < 0.001); however, neither low-dose acetazolamide nor saline induced preretinal neovascularization. CONCLUSIONS: Acidosis induced by high-dose acetazolamide, independent of hyperoxemia or hypoxemia, is associated with preretinal neovascularization in the neonatal rat. Induction of neovascularization appears to depend on a critical threshold of acidosis severity. This study further supports a proposed independent role for acidosis in the pathogenesis of ROP.

Acetazolamide↗

PubMed2000

Norian craniofacial repair system bone cement for the repair of craniofacial skeletal defects.

PURPOSE: To describe the use of the Norian Craniofacial Repair System (CRS) calcium phosphate bone cement in the restoration of craniofacial skeletal defects. METHODS: Consecutive case series. RESULTS: Calcium phosphate bone cement was used to repair craniofacial skeletal defects in three patients. Indications included repair of a posttraumatic orbital floor defect causing hypo-ophthalmos, reconstruction of frontal craniotomy and temporalis muscle donor sites in a patient who had undergone resection of an invasive squamous cell carcinoma, and augmentation of a post-traumatic anterior maxillary skeletal defect. The primary outcome measure was the restoration of bony volume and support. The use of calcium phosphate bone cement in these patients was effective and without complications. CONCLUSIONS: Norian CRS calcium phosphate bone cement is useful in the repair of craniofacial skeletal defects.

Adult↗

PubMed2000

Neovascularization grading methods in a rat model of retinopathy of prematurity.

PURPOSE: The method of counting cell nuclei above the internal limiting membrane in histologic sections is considered the standard when quantifying neovascularization (NV) in rodent oxygen-induced retinopathy (OIR). An alternative, more rapid method of counting clock hours in flatmounted adenosine diphosphatase (ADPase)-stained rat retinas is analogous to clinically scoring retinopathy of prematurity (ROP). In the present study, the validity of counting clock hours was evaluated by a direct comparison of these techniques. The intereye correlation of NV score and retinal vascular area were also studied. METHODS: Newborn Sprague-Dawley rats were exposed to cycles of O2 (80-10%) for 7 days, followed by 5 days of room air recovery. Preretinal NV was quantified by three masked observers counting clock hours in flatmounted ADPase-stained retinas of both eyes. Retinal vascular and total retinal areas were calculated using computer-assisted analysis. Representative retinas that had been scored positive (n = 10) and negative (n = 3) for NV and room air control retinas (n = 3) were embedded in paraffin. Each entire peripheral retinal quadrant was serially sectioned at 6 microm and stained with hematoxylin and eosin. Nuclei above the internal limiting membrane were then counted in a masked manner. The total number of nuclei counted per retina was defined as the nucleus count (704-938 sections per retina; 12,900 sections). Correlations were evaluated using Spearman rank coefficients. RESULTS: The nucleus count was 0 to 44 in room air control retinas, 0 to 40 in negative OIR retinas, and 250 to 5634 in positive OIR retinas. The nucleus count was highly correlated with the clock hour score (r(s) = 0.95, P = 0.0001). For the paired retinas, there was a significant correlation between right and left eyes in the severity of NV (clock hours; r(s) = 0.76, P = 0.0001) and the ratio of retinal vascular area to total retinal area (r(s) = 0.81, P = 0.0001). CONCLUSIONS: The more rapid method of counting clock hours in flatmounted ADPase-stained retinas is valid for quantifying NV in rat models of ROP. Incidence and severity of NV and vascularized areas were similar between left and right eyes, which permits the use of paired retinas for complementary research techniques.

Animals↗

PubMed2000

Botulinum toxin treatment versus conservative management in acute traumatic sixth nerve palsy or paresis.

PURPOSE: Botulinum toxin (BTX), injected into the ipsilateral medial rectus muscle, has been advocated for the management of acute traumatic sixth nerve palsy or paresis. We conducted a multicenter, nonrandomized, data collection study to evaluate recovery rates of patients treated with either conservative measures or BTX. METHODS: All members of the American Association for Pediatric Ophthalmology and Strabismus and the North American Neuro-Ophthalmology Society were invited to enroll patients with acute traumatic sixth nerve palsy or paresis during a 2-year period (between March 1996 and February 1998). The BTX group was defined as patients who received a BTX injection within 3 months of injury. Recovery at 6 months from injury was defined as absence of diplopia in the primary position and a distance esotropia of no more than 10 PD in the primary position. Nonrecovered patients with less than 6 months of follow-up (n = 15) were excluded. RESULTS: Eighty-four eligible patients were enrolled by 46 investigators. Sixty-two patients (74%) were treated conservatively and 22 (26%) with BTX. Sixty-two patients (74%) had unilateral palsy, and 22 (26%) had bilateral palsy. Recovery rates were similar between BTX and conservatively treated patients (overall: 73% vs 71%, P = 1.0; unilateral: 81% vs 83%, P = 1.0; bilateral: 50% vs 38%, P = 0.66, respectively). CONCLUSIONS: In this prospective multicenter study of acute traumatic sixth nerve palsy or paresis, patients treated with either BTX or conservative measures had similar high recovery rates.

Abducens Nerve Injury↗

PubMed1999

Pediatric third, fourth, and sixth nerve palsies: a population-based study.

PURPOSE: To determine the population-based incidence and cause of cranial nerve palsies affecting ocular motility in children in the circumscribed population of Olmsted County, Minnesota. METHODS: The Rochester Epidemiology Project medical records linkage system captures virtually all medical care provided to Olmsted County residents. By means of this database, all cases of third, fourth, and sixth cranial nerve palsy were identified among county residents less than 18 years of age from 1978 through 1992. Medical records were reviewed to confirm the diagnosis, determine the cause, and document county residency. Incidence rates were adjusted to the age and sex distribution of the 1990 white population in the United States. RESULTS: Over this 15-year period, 36 incidence cases of cranial nerve palsy were identified in 35 children in this defined population. The age-adjusted and sex-adjusted annual incidence of third, fourth, and sixth nerve palsies combined was 7.6 per 100,000 (95% confidence interval, 5.1 to 10.1). The most commonly affected nerve was the fourth (36%), followed by the sixth (33%), the third (22%), and multiple nerve palsies (9%). The most common cause was congenital for third and fourth nerve palsy, undetermined for sixth, and trauma for multiple nerve palsies. Although three cases were associated with neoplasia, a cranial nerve palsy was not present at the time of diagnosis in any case. CONCLUSIONS: Unlike many institutionally based referral series, our population-based study provides data on the incidence and cause of third, fourth, and sixth nerve palsies in a geographically defined population. In contrast to previous institutionally based series, nearly half the cases were congenital in origin, and in no case did intracranial neoplasia present as an isolated nerve palsy.

Abducens Nerve↗

PubMed1999

Shortening properties of two biochemically defined muscle fibre types of the Norway lobster Nephrops norvegicus L.

Mechanical properties of myofibrillar bundles from single chemically skinned fibres from the superficial abdominal flexor muscle of the Norway lobster Nephrops norvegicus were measured, and the protein content of these fibres was analysed by SDS-PAGE. Two slow fibre phenotypes (S1, S2) were distinguished on the basis of their myofibrillar protein assemblages. Data from 9 S1 and 8 S2 fibres obtained at similar sarcomere length demonstrate significant differences between the fibre types in maximal tension (N cm-2, S1: 10.5 +/- 3.9; S2: 3.1 +/- 0.8), in the delay of the peak of stretch activation (ms, S1: 122 +/- 18; S2: 412 +/- 202), in fibre stiffness (N cm-2 per nm half sarcomere, S1: 0.36 +/- 0.19; S2: 0.09 +/- 0.03) and in maximal shortening velocity (fibre length s-1, S1: 0.53 +/- 0.10; S2: 0.27 +/- 0.06). Furthermore, the maximal power output of the type S1 fibres was about five times larger than that of S2 fibres. The power output was maximal at lower loads in S1 fibres (relative load = 0.37 +/- 0.04) than in S2 fibres (relative load = 0.44 +/- 0.05). This study represents a comprehensive investigation of two slow muscle fibre types which are thought to be specialized for slow movements (S1 fibres) and for the postural control of the abdomen (S2 fibres).

Animals↗

PubMed1999

Metabolic acidosis-induced retinopathy in the neonatal rat.

PURPOSE: Carbon dioxide (CO2)-induced retinopathy (CDIR) in the neonatal rat, analogous to human retinopathy of prematurity (ROP), was previously described by our group. In this model, it is possible that CO2-associated acidosis provides a biochemical mechanism for CDIR. Therefore, the effect of pure metabolic acidosis on the developing retinal vasculature of the neonatal rat was investigated. METHODS: A preliminary study of arterial blood pH was performed to confirm acidosis in our model. In neonatal rats with preplaced left carotid artery catheters, acute blood gas samples were taken 1 to 24 hours after gavage with either NH4Cl 1 millimole/100 g body weight or saline. In the subsequent formal retinopathy study, 150 newborn Sprague-Dawley rats were raised in litters of 25 and randomly assigned to be gavaged twice daily with either NH4Cl 1 millimole/100 g body weight (n = 75) or saline (n = 75) from day 2 to day 7. After 5 days of recovery, rats were killed, and retinal vasculature was assessed using fluorescein perfusion and ADPase staining techniques. RESULTS: In the preliminary pH study, the minimum pH after NH4Cl gavage was 7.10+/-0.10 at 3 hours (versus 7.37+/-0.03 in controls, mean +/- SD, P < 0.01). In the formal retinopathy study, preretinal neovascularization occurred in 36% of acidotic rats versus 5% of controls (P < 0.001). Acidotic rats showed growth retardation (final weight 16.5+/-3.0 g versus 20.2+/-2.6 g, P < 0.001). The ratio of vascularized to total retinal area was smaller in acidotic rats (94%+/-4% versus 96%+/-2%, P < 0.001). CONCLUSIONS: Metabolic acidosis alone induces neovascularization similar to ROP in the neonatal rat. This suggests a possible biochemical mechanism by which high levels of CO2 induce neovascularization and supports the suggestion that acidosis may be an independent risk factor for ROP.

Acidosis↗